free-radicals-chemical-biology-from-chemical-behavior-to-biomarker

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development

The involvement of free radicals in life sciences has constantly increased with time and has been connected to several physiological and pathological ...

Consiglio Nazionale delle Ricerche

Para obtener informaci&oacute;n sobre la actividad mostrada por an&aacute;logos de alfa-p&eacute;ptido/beta-sulfonamidopeptide h&iacute;brido de la potente agente quimiot&aacute;ctico fMLF-OMe, un estudio de la estructura y actividad se divulga en modelos de trip&eacute;ptido N-Boc - y N-formil que contiene un &aacute;cido aminoalkanesulfonic como residuo central. Se han medido migraci&oacute;n dirigida (quimiotaxis), la producci&oacute;n de ani&oacute;n super&oacute;xido y la liberaci&oacute;n de la lisozima. Las funciones bioqu&iacute;micas y las propiedades conformacionales de los nuevos compuestos se discute y se relaciona con modelos previamente estudiados que contengan residuos de beta.

Alfa-p&eacute;ptido/beta-sulfonamidopeptide h&iacute;bridos: an&aacute;logos de la agente quimiot&aacute;ctico para-Met-Leu-Phe-OMe.

In order to gain information on the activity shown by alpha-peptide/beta-sulfonamidopeptide hybrid analogs of the potent chemotactic agent fMLF-OMe, a structure-activity study is reported on N-Boc- and N-formyl tripeptide models containing an aminoalkanesulfonic acid as central residue. Directed migration (chemotaxis), superoxide anion production, and lysozyme release have been measured. The biochemical functions and the conformational properties of the new compounds are discussed and related to previously studied models containing beta-residues.

Alpha-peptide/beta-sulfonamidopeptide hybrids: analogs of the chemotactic agent for-Met-Leu-Phe-OMe.

Afin d&#39;obtenir des informations sur l&#39;activit&eacute; illustr&eacute;e par des analogues d&#39;alpha-peptide/b&ecirc;ta-sulfonamidopeptide hybride de l&#39;agent chimiotactique puissante fMLF-OMe, une &eacute;tude de la structure et l&#39;activit&eacute; est signal&eacute;e sur les mod&egrave;les de tripeptide N-Boc - et N-formyl contenant un acide aminoalkanesulfonic comme r&eacute;sidu central. Ont a mesur&eacute; les migrations dirig&eacute;e (chimiotactisme), production d&#39;anions superoxyde et lysozyme release. Les fonctions biochimiques et les propri&eacute;t&eacute;s conformationnelles des nouveaux compos&eacute;s sont discut&eacute;es et associ&eacute;es &agrave; des mod&egrave;les &eacute;tudi&eacute;s pr&eacute;c&eacute;demment contenant des r&eacute;sidus de b&ecirc;ta.

Alpha-peptide/b&ecirc;ta-sulfonamidopeptide hybrides : analogues de l&#39;agent chimiotactique pour-Met-Leu-Phe-OMe.

Al fine di ottenere informazioni sull&#39;attivit&agrave; mostrata da analoghi alfa-peptide/beta-sulfonamidopeptide ibrida del potente agente chemiotattico fMLF-OMe, uno studio di struttura-attivit&agrave; &egrave; riportato sui modelli di tripeptide Boc-N - e N-formil contenente un acido aminoalkanesulfonic come residuo centrale. Regia migrazione (chemiotassi), produzione di anione superossido e lisozima release sono stati misurati. Le funzioni biochimiche e le propriet&agrave; conformazionali di nuovi composti sono discusse e relative ai modelli precedentemente studiati contenenti residui di beta.

Alfa-peptide/beta-sulfonamidopeptide ibridi: analoghi dell&#39;agente chemiotattico per-Met-Leu-Phe-OMe.

Peptide derivatives 1-5, incorporating synthetic non-proteinogenic amino acids, related to the beta-amyloid 17-21 fragment of the amyloidogenic Abeta(1-40), and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by using Soto's pentapeptide Ac-LPFFD-NH(2) (iAbeta5p) as lead compound. Their activity as inhibitors of fibrillogenesis and stability against enzymatic degradation have been determined. Compounds 1, 5 and 6 are potent inhibitors in comparison to the lead compound. Exposure to chymotrypsin of peptide derivatives 1-5, all containing unnatural amino acids, shows increased stability as compared with iAbeta5p and 6. Conformational properties of the new compounds have been determined by CD and FT-IR spectroscopies.

Synthesis and activity of fibrillogenesis peptide inhibitors related to the 17-21 beta-amyloid sequence.

D&eacute;riv&eacute;s de peptide 1-5, incorporant synth&eacute;tique non-acide amin&eacute;, associ&eacute;s &agrave; la prot&eacute;ine b&ecirc;ta-amylo&iuml;de, 17-21 fragments de l&#39;amylo&iuml;dog&egrave;ne Abeta(1-40) et le d&eacute;capeptide prot&eacute;g&eacute; N 6, correspondant &agrave; une s&eacute;quence dim&egrave;re du m&ecirc;me fragment, ont &eacute;t&eacute; synth&eacute;tis&eacute;s. Ces compos&eacute;s ont &eacute;t&eacute; con&ccedil;us en utilisant le pentapeptide de Soto Ac-LPFFD-NH(2) (iAbeta5p) comme principal compos&eacute;. Leur activit&eacute; en tant qu&#39;inhibiteurs de FIBRILLOGENESE et de la stabilit&eacute; contre la d&eacute;gradation enzymatique ont &eacute;t&eacute; d&eacute;termin&eacute;es. Compos&eacute;s de 1, 5 et 6 sont de puissants inhibiteurs en comparaison avec le compos&eacute; principal. Exposition &agrave; la chymotrypsine, de d&eacute;riv&eacute;s de peptide 1-5, tous contenant des acides amin&eacute;s non naturels, montre une stabilit&eacute; accrue par rapport aux iAbeta5p et 6. Propri&eacute;t&eacute;s conformationnelles des nouveaux compos&eacute;s ont &eacute;t&eacute; d&eacute;termin&eacute;es par spectroscopie FT-IR et CD.

La synth&egrave;se et l&#39;activit&eacute; des inhibiteurs de peptide FIBRILLOGENESE associ&eacute;s &agrave; la s&eacute;quence de prot&eacute;ines b&ecirc;ta-amylo&iuml;des 17-21.

Derivati del peptide 1-5, che incorporano gli aminoacidi sintetici non proteinogenici, correlati a beta-amiloide frammento 17-21 di amiloidogeniche Abeta(1-40) e il decapeptide protetto N 6, corrispondente a una sequenza dimerica dello stesso frammento, sono stati sintetizzati. Questi composti sono stati progettati utilizzando pentapeptide di Soto Ac-LPFFD-NH(2) (iAbeta5p) come composto di piombo. Loro attivit&agrave; come inibitori di fibrillogenesis e stabilit&agrave; contro degradazione enzimatica sono stati determinati. Composti di 1, 5 e 6 sono potenti inibitori rispetto ai composto del piombo. L&#39;esposizione a chimotripsina dei derivati del peptide 1-5, tutti contenenti amminoacidi innaturali, mostra maggiore stabilit&agrave; rispetto ai iAbeta5p e 6. Propriet&agrave; conformazionali di nuovi composti sono stati determinati dalla spettroscopia CD e FT-IR.

Sintesi e l&#39;attivit&agrave; degli inibitori del peptide fibrillogenesis legato alla sequenza di beta-amiloide 17-21.

Derivados del p&eacute;ptido 1-5, incorporaci&oacute;n de amino&aacute;cidos sint&eacute;ticos no-proteinogenic, relacionado con el beta-amiloide fragmento 17-21 de la amyloidogenic Abeta(1-40) y el decap&eacute;ptido protegido N 6, correspondiente a una secuencia dim&eacute;rica del mismo fragmento, han sido sintetizados. Estos compuestos fueron dise&ntilde;ados usando pentap&eacute;ptido de Soto Ac-LPFFD-NH(2) (iAbeta5p) como compuesto de plomo. Se ha determinado su actividad como inhibidores de fibrilog&eacute;nesis y estabilidad contra la degradaci&oacute;n enzim&aacute;tica. Los compuestos 1, 5 y 6 son inhibidores potentes en comparaci&oacute;n con el compuesto de plomo. Exposici&oacute;n a la quimotripsina de derivados del p&eacute;ptido 1-5, todos conteniendo amino&aacute;cidos antinaturales, muestra mayor estabilidad en comparaci&oacute;n con iAbeta5p y 6. Propiedades conformacionales de los nuevos compuestos han sido determinadas por espectroscop&iacute;as de CD y FT-IR.

S&iacute;ntesis y actividad de fibrilog&eacute;nesis inhibidores de p&eacute;ptido relacionado con la secuencia de la prote&iacute;na beta-amiloide de 17-21.

The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe-NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3-pyrrolidinesulphonic acid (betaPrs) have been synthesized and their binding affinity and functional activity have been investigated. The highest micro-receptor affinity is shown by [(S)betaPrs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of opioid peptides.

Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.

Les endomorphines agonistes opio&iuml;des (Tyr-Pro-Trp-Phe-NH(2) ; EM1 et Tyr-Pro-Phe-Phe-NH(2) ; EM2) et morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) pi&egrave;ce une s&eacute;lectivit&eacute; tr&egrave;s &eacute;lev&eacute;e pour le r&eacute;cepteur mu-opio&iuml;de. Ici, une s&eacute;rie de roman EM2 et morphiceptin analogues contenant en lieu et place de la proline &agrave; la position 2 de la S et R les r&eacute;sidus de b&ecirc;ta-homologues de la proline (HPro), de l&#39;acide 2-pyrrolidinemethanesulphonic (HPR) et de l&#39;acide 3-pyrrolidinesulphonic (betaPrs) ont &eacute;t&eacute; synth&eacute;tis&eacute;s et leur affinit&eacute; de liaison et l&#39;activit&eacute; fonctionnelle ont &eacute;t&eacute; &eacute;tudi&eacute;s. L&#39;affinit&eacute; du r&eacute;cepteur micro plus haute t&eacute;moignent [(S)betaPrs(2)] EM2 analogique (6e), qui repr&eacute;sente le premier exemple d&#39;un analogue de la b&ecirc;ta-sulphonamido dans le domaine des peptides opio&iuml;des.

Synth&egrave;se et activit&eacute; d&#39;endomorphine-2 et morphiceptin analogues des substituts de la proline en position 2.

Gli oppioidi agonisti endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 e Tyr-Pro-Phe-Phe-NH(2); EM2) e morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) Mostra un&#39;elevatissima selettivit&agrave; per il recettore mu-oppioide. Qui una serie di romanzo EM2 e morphiceptin analoghi contenenti al posto della prolina in posizione 2 S e R residui di beta-omologhi di prolina (HPro), dell&#39;acido 2-pyrrolidinemethanesulphonic (HPrs) e di acido 3-pyrrolidinesulphonic (betaPrs) sono stati sintetizzati e loro affinit&agrave; di legame e l&#39;attivit&agrave; funzionale sono stati indagati. il pi&ugrave; alta affinit&agrave; di micro-recettore &egrave; mostrato da EM2 [(S)betaPrs(2)] analogico (6e) che rappresenta il primo esempio di un analogo beta-sulphonamido nel campo dei peptidi oppioidi.

Sintesi e attivit&agrave; di endomorphin-2 e morphiceptin analoghi con surrogati di prolina in posizione 2.

El endomorphins de agonistas opi&aacute;ceos (Tyr-Pro-Trp-Phe-NH(2); EM1 y Tyr-Pro-Phe-Phe-NH(2); EM2) y morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) muestra una extremadamente alta selectividad para los receptores mu-opioides. Aqu&iacute; una serie de novela EM2 y an&aacute;logos de morphiceptin que contiene en lugar de la prolina en la posici&oacute;n 2 de los residuos S y R de beta-hom&oacute;logos de prolina (HPro), del &aacute;cido 2-pyrrolidinemethanesulphonic (HPR) y del &aacute;cido 3-pyrrolidinesulphonic (betaPrs) han sido sintetizados y su afinidad y actividad funcional han sido investigados. La mayor afinidad de micro receptor se muestra por [(S)betaPrs(2)] EM2 an&aacute;logo (6e) que representa el primer ejemplo de un an&aacute;logo de la beta-sulphonamido en el campo de los p&eacute;ptidos opioides.

S&iacute;ntesis y actividad de endomorphin-2 y morphiceptin an&aacute;logos con sustitutos de la prolina en la posici&oacute;n 2.

Combining various techniques in solution we proved that Doxorubicin, also called Adriamycin, and Sabarubicin, also known as MEN 10755, bind to the human telomeric sequence, 5'-d[GGG(TTAGGG)(3)]-3' (21-mer), assuming a G-quadruplex structure in the presence of K(+). Complexes of drugs with the 21-mer in 1â€‰:â€‰1 and 2â€‰:â€‰1 stoichiometry coexist in solution. Association constants were obtained from titration experiments and confirmed by isothermal titration calorimetry. The fluorescence of the drugs was quenched upon complexation. UV circular dichroism (CD) spectra of the complexes were characterized by the G-quadruplex signal and indicated that drug binding influences the equilibrium between quadruplex conformations. The visible CD spectra were exclusively due to the drug and show differences in the complexation modes of the two drugs. Spectroscopic and thermodynamic parameters of the 1â€‰:â€‰1 complexes point to drug stacking with the G-quadruplex top or bottom tetrad. Thermodynamic data suggests that the binding of the second drug molecule in the 2â€‰:â€‰1 complex may occur in a groove. Complexation caused a small increase in the thermal stability of the G-quadruplex main conformation, shifting T(m) from 62 to 67 Â°C.

Affinity of the anthracycline antitumor drugs Doxorubicin and Sabarubicin for human telomeric G-quadruplex structures.

Combinant diff&eacute;rentes techniques dans la solution, nous avons prouv&eacute; que la doxorubicine, &eacute;galement appel&eacute;e adriamycine et Sabarubicin, &eacute;galement connu comme hommes 10755, lient &agrave; la s&eacute;quence t&eacute;lom&eacute;rique humaine, 5&#39;-d[GGG(TTAGGG)(3)] -3 &#39; 21 (outre-mer), en supposant un G-quadruplexe structurer en pr&eacute;sence de k. Complexes de m&eacute;dicaments avec la mer-21 1:1 et 2: 1 stoechiom&eacute;trie coexistent dans la solution. Constantes d&#39;association ont &eacute;t&eacute; obtenus &agrave; partir des exp&eacute;riences de titrage et confirm&eacute;es par calorim&eacute;trie isotherme de titration. La fluorescence des m&eacute;dicaments &eacute;tait tremp&eacute;e &agrave; la complexation. Les spectres UV de dichro&iuml;sme circulaire (CD) des complexes ont &eacute;t&eacute; caract&eacute;ris&eacute;s par le signal G-quadruplexe et a indiqu&eacute; que la liaison m&eacute;dicament influe sur l&#39;&eacute;quilibre entre les conformations quadruplex. Les spectres visibles de CD ont &eacute;t&eacute; exclusivement due aux drogue et voir la diff&eacute;rences dans les modes de complexation des deux m&eacute;dicaments. Param&egrave;tres spectroscopiques et thermodynamiques des complexes 1: 1 point &agrave; empiler avec la t&eacute;trade de haut ou en bas de G-quadruplexe de drogue. Donn&eacute;es thermodynamiques sugg&egrave;rent que la liaison de la mol&eacute;cule du m&eacute;dicament deuxi&egrave;me dans le complexe de 2: 1 peut se produire dans une rainure. Complexation a caus&eacute; une l&eacute;g&egrave;re augmentation dans la stabilit&eacute; thermique de la conformation principale de G-quadruplexe, transfert T(m) de 62 &agrave; 67 &deg; C.

L&#39;affinit&eacute; de l&#39;anthracycline antitumorale m&eacute;dicaments doxorubicine et Sabarubicin pour les structures de G-quadruplexe t&eacute;lom&eacute;riques humaines.

Combinazione di varie tecniche in soluzione abbiamo dimostrato che doxorubicina, chiamato anche Adriamicina e Sabarubicin, anche conosciuto come uomini 10755, associare alla sequenza telomeric umana, 5&#39;-d[GGG(TTAGGG)(3)] -3 &#39; (21-mer), assumendo un G-quadruplex struttura in presenza di K(+). Complessi di farmaci con la mer 21 in 1:1 e 2: 1 stechiometria coesistono in soluzione. Costanti di associazione sono stati ottenuti da esperimenti di titolazione e confermate dalla calorimetria isotermica di titolazione. La fluorescenza delle droghe &egrave; stata temprata alla complessazione. Gli spettri di Dicroismo circolare (CD) UV dei complessi erano caratterizzati dal segnale di G-quadruplex e indicati che associazione farmaco influenza l&#39;equilibrio tra quadruplex conformazioni. Gli spettri CD visibili erano esclusivamente a causa della droga e Visualizza differenze nelle modalit&agrave; di complessazione dei due farmaci. Parametri termodinamici e spettroscopici dei complessi 1: 1 punto a farmaco di sovrapposizione con la tetrade di G-quadruplex superiore o inferiore. Dati termodinamici suggeriscono che l&#39;associazione della molecola del farmaco seconda nel complesso 2: 1 pu&ograve; verificarsi in un solco. Complessazione ha causato un piccolo aumento della stabilit&agrave; termica di conformazione principale del G-quadruplex, spostando T(m) da 62 a 67 &deg; C.

Affinit&agrave; tra l&#39;antraciclina antitumorale farmaci doxorubicina e Sabarubicin per le strutture di G-quadruplex telomeric umani.

Combinando diferentes t&eacute;cnicas en la soluci&oacute;n que hemos podido comprobar que la doxorrubicina, tambi&eacute;n llamado adriamicina y Sabarubicin, tambi&eacute;n conocido como hombres 10755, se unen a la secuencia telom&eacute;rica humana, 5&#39;-d[GGG(TTAGGG)(3)] -3 &#39; (21-mer), suponiendo un G-quadruplex estructura en presencia de capacidad. Complejos de drogas con el mer de 21 en 1:1 y 2: 1 estequiometr&iacute;a coexisten en soluci&oacute;n. Constantes de asociaci&oacute;n fueron obtenidos de experimentos de titulaci&oacute;n y confirmadas por calorimetr&iacute;a isoterma de titulaci&oacute;n. La fluorescencia de las drogas fue saciada con complejaci&oacute;n. Los espectros de dicro&iacute;smo circular (CD) Ultravioleta de los complejos fueron caracterizados por la se&ntilde;al de G-quadruplex e indic&oacute; que Uni&oacute;n de drogas influye en el equilibrio entre quadruplex conformaciones. El espectro visible de la CD fueron exclusivamente debido a las drogas y mostrar diferencias en los modos de la complejaci&oacute;n de los dos f&aacute;rmacos. Par&aacute;metros espectrosc&oacute;picos y termodin&aacute;micos de los complejos 1: 1 punto a apilar con la t&eacute;trada quadruplex G de la parte superior o inferior de la droga. Datos termodin&aacute;micos sugieren que la Uni&oacute;n de la segunda mol&eacute;cula de droga en el complejo de 2: 1 puede ocurrir en una ranura. Complejaci&oacute;n caus&oacute; un peque&ntilde;o aumento en la estabilidad t&eacute;rmica de la conformaci&oacute;n principal G-quadruplex, cambio T(m) de 62 a 67 &deg; C.

Afinidad de la antraciclina antitumoral drogas doxorrubicina y Sabarubicin para estructuras humanas de G-quadruplex telom&eacute;ricas.

Un porphyrazine de Zn(II) soluble en agua conduce el equilibrio conformacional de la G-quadruplex de una secuencia telom&eacute;rica humana exclusivamente hacia una conformaci&oacute;n paralela a la complejaci&oacute;n.

Un porphyrazine Zn(II) cati&oacute;nico induce una conformaci&oacute;n de G-quadruplex paralela estable en ADN telom&eacute;rico humano.

A water soluble Zn(II) porphyrazine drives the conformational equilibrium of the G-quadruplex of a human telomeric sequence exclusively towards a parallel conformation upon complexation.

A cationic Zn(II) porphyrazine induces a stable parallel G-quadruplex conformation in human telomeric DNA.

Un porphyrazine de Zn (II) soluble dans l&#39;eau entra&icirc;ne l&#39;&eacute;quilibre conformationnel de la G-quadruplexe d&#39;une s&eacute;quence t&eacute;lom&eacute;rique humaine exclusivement vers une conformation parall&egrave;le &agrave; la complexation.

Un porphyrazine cationique de Zn (II) induit une conformation stable de G-quadruplexe parall&egrave;le en ADN t&eacute;lom&eacute;rique humaine.

Un porphyrazine di Zn(II) solubile in acqua spinge l&#39;equilibrio conformazionale di G-quadruplex di una sequenza telomeric umana esclusivamente verso una conformazione parallela alla complessazione.

Un porphyrazine Zn(II) cationico induce una conformazione stabile di G-quadruplex parallela nel DNA telomeric umano.

We studied the binding of two anthracycline drugs, Doxorubicin and Sabarubicin, to a model telomeric sequence 5'-d[GGG(TTAGGG)(3)]-3' (21-mer), assuming the basket G-quadruplex (G4) conformation in Na(+)-rich aqueous solution. We used an approach that combines spectroscopic and microcalorimetric techniques to obtain information about ground and excited state properties of the most stable complexes. Both drugs bind to the 21-mer in basket conformation and complexes of 1:1 and 2:1 drug : 21-mer stoichiometry coexist in solution. Binding constants were determined from fluorescence and isothermal titration calorimetry experiments. For both drugs association is driven by enthalpy and disfavoured by entropy in the case of two sequential binding events to different sites. The drug fluorescence is completely quenched in the 1:1 complex, most likely by electron transfer from the guanine system to the anthraquinone moiety, while part of the emission survives in the 2:1 complex. Circular dichroism (CD) of the individual complexes is dominated by the G-quadruplex signal in the UV and by the anthracycline signal in the near-UV and Vis region. The experimental CD spectra combined with conformational calculations at MM level and quantum mechanical calculation of the rotational strength of the electronic transitions afforded information on the binding geometries.

Complexes of the antitumoral drugs Doxorubicin and Sabarubicin with telomeric G-quadruplex in basket conformation: ground and excited state properties.

Nous avons &eacute;tudi&eacute; la liaison de deux m&eacute;dicaments anthracycline, doxorubicine et Sabarubicin, &agrave; un mod&egrave;le s&eacute;quence t&eacute;lom&eacute;rique 5&#39;-d[GGG(TTAGGG)(3)] -3 &#39; 21 (outre-mer), en supposant que le panier de conformation G-quadruplexe (G4) na (+)-riche en solution aqueuse. Nous avons utilis&eacute; une approche qui combine spectroscopiques et microcalorim&eacute;triques techniques pour obtenir des informations sur le sol et les propri&eacute;t&eacute;s des &eacute;tats excit&eacute;s des complexes plus stables. Les deux m&eacute;dicaments se lient &agrave; la 21-mer dans la conformation du panier et complexes de drogue 1:1 et 2:1:21-mer stoechiom&eacute;trie coexistent dans la solution. Les constantes de fixation ont &eacute;t&eacute; d&eacute;termin&eacute;es de fluorescence et des exp&eacute;riences de calorim&eacute;trie isotherme de titration. Pour les deux m&eacute;dicaments association d&eacute;pend de l&#39;enthalpie et d&eacute;favorise par entropie dans le cas de deux &eacute;v&eacute;nements de liaison s&eacute;quentielle &agrave; des sites diff&eacute;rents. La fluorescence de la drogue est compl&egrave;tement tremp&eacute;e dans le complexe, tr&egrave;s probablement par transfert d&#39;&eacute;lectrons provenant du syst&egrave;me de la guanine en sa portion de l&#39;anthraquinone, 1:1, tandis que la partie de l&#39;&eacute;mission survit dans le 2:1 complexe. Dichro&iuml;sme circulaire (CD) des complexes individuels est domin&eacute;e par le signal G-quadruplexe dans l&#39;UV et par le signal de l&#39;anthracycline dans la r&eacute;gion de la Vis et le proche UV. Des spectres exp&eacute;rimentaux de CD combin&eacute; avec des calculs conformationnels au MM niveau et calcul de m&eacute;canique quantique de la force rotationnelle des transitions &eacute;lectroniques fournit des informations sur les g&eacute;om&eacute;tries de liaison.

Complexes des m&eacute;dicaments antitumoraux doxorubicine et Sabarubicin avec G-quadruplexe t&eacute;lom&eacute;rique en conformation panier : propri&eacute;t&eacute;s de l&#39;&eacute;tat fondamental et excit&eacute;.

Abbiamo studiato l&#39;associazione di due farmaci antraciclina, doxorubicina e Sabarubicin, a un modello sequenza telomerica 5&#39;-d[GGG(TTAGGG)(3)] -3 &#39; (21-mer), supponendo che il cestello conformazione G-quadruplex (G4) na (+)-soluzione acquosa ricca. Abbiamo usato un approccio che combina spettroscopiche e microcalorimetric tecniche per ottenere informazioni sul terreno e stato eccitato propriet&agrave; dei complessi pi&ugrave; stabili. Entrambi i farmaci si legano a 21-mer nella conformazione del cestello e complessi della droga 1:1 e 2:1:21-mer stechiometria coesistono in soluzione. Costanti di associazione sono stati determinati da esperimenti di calorimetria isotermica di titolazione e fluorescenza. Per entrambi i farmaci associazione &egrave; guidata da entalpia e natura di entropia nel caso di due eventi di associazione sequenziale di diversi siti. La fluorescenza di droga &egrave; completamente spenta nel complesso, molto probabilmente dal trasferimento di elettroni dal sistema di guanina del moiety antrachinonici, 1:1 mentre parte dell&#39;emissione sopravvive in 2:1 complessi. Dicroismo circolare (CD) dei singoli complessi &egrave; dominato dal segnale di G-quadruplex nell&#39;UV e dal segnale di antraciclina nel vicino UV Vis regione. Gli spettri CD sperimentali combinano con calcoli conformazionali a livello MM e calcolo meccanica quantistica della forza rotazionale di transizioni elettroniche offerte informazioni sulle geometrie di associazione.

Complessi dei farmaci antitumorali doxorubicina e Sabarubicin con G-quadruplex telomerica nella conformazione del cestello: propriet&agrave; dello stato eccitato e rettificato.

Estudiamos la Uni&oacute;n de dos f&aacute;rmacos de antraciclina, doxorrubicina y Sabarubicin, a un modelo secuencia telom&eacute;rica 5&#39;-d[GGG(TTAGGG)(3)] -3 &#39; (21-mer), asumiendo la cesta G-quadruplex (G4) conformaci&oacute;n en Na (+)-soluci&oacute;n acuosa Rica. Utilizamos un enfoque que combina espectrosc&oacute;picas y t&eacute;cnicas de microcalorimetric para obtener informaci&oacute;n sobre la tierra y las propiedades de estado excitado de los complejos m&aacute;s estables. Ambos f&aacute;rmacos se unen a los 21-mer en la conformaci&oacute;n de la cesta y complejos de droga 1:1 y 2:1:21-mer estequiometr&iacute;a conviven en soluci&oacute;n. Enlace constantes determinaron de fluorescencia y experimentos de calorimetr&iacute;a de titulaci&oacute;n isot&eacute;rmica. Para ambos f&aacute;rmacos asociaci&oacute;n es impulsada por la entalpia y desfavorecida por la entrop&iacute;a en el caso de dos eventos de enlace alternativamente a diferentes sitios. La fluorescencia de la droga se apaga completamente en el complejo, probablemente por la transferencia de electrones desde el sistema de la guanina a la mol&eacute;cula de antraquinona, de 1:1, mientras que parte de la emisi&oacute;n sobrevive en el 2:1 complejo. Dicro&iacute;smo circular (CD) de los complejos individuales est&aacute; dominado por la se&ntilde;al de G-quadruplex en la UV y la se&ntilde;al de antraciclina en la regi&oacute;n de Vis y cerca de UV. Los espectros experimentales de CD combinan con c&aacute;lculos conformacionales nivel MM y c&aacute;lculo mec&aacute;nico cu&aacute;ntico de la fuerza rotacional de las transiciones electr&oacute;nicas que brinda informaci&oacute;n sobre las geometr&iacute;as de la Uni&oacute;n.

Complejos de los f&aacute;rmacos antitumorales doxorrubicina y Sabarubicin con G-quadruplex telom&eacute;rica en la conformaci&oacute;n de la cesta: propiedades de estado de la tierra y emocionado.

The behavior of a bimetallic water-soluble (Zn(II)/Pt(II)) porphyrazine hexacation as ligand of G-quadruplex (G4) structures adopted by a human telomeric DNA sequence has been examined with different spectroscopic techniques. In K(+) rich solution the hexacationic Zn(II) porphyrazine ligand bearing a peripheral cis-platin-like functionality changes the G-quadruplex conformational equilibrium of the human telomeric sequence 5'-d[AGGG(TTAGGG)(3)]-3' and drives it exclusively toward a very stable parallel G4 form in the complex with 2:1 stoichiometry. An increase of the melting temperature of more than 20 Â°C is observed in this complex compared to the G4 alone. On the contrary ligand binding to G-quadruplex of the same telomeric sequence in Na(+) rich solution neither markedly influences the predominant basket conformation nor confers increased thermal stability to the G4 structure.

Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 10. A water-soluble bimetallic (Zn(II)/Pt(II)) porphyrazine hexacation as potential plurimodal agent for cancer therapy: exploring the behavior as ligand of telomeric DNA G-quadruplex structures.

Le comportement d&#39;un bilame solubles dans l&#39;eau (Zn(II)/Pt(II)) porphyrazine hexacation comme ligand des structures G-quadruplexe (G4), adopt&eacute; par une s&eacute;quence d&#39;ADN t&eacute;lom&eacute;rique a &eacute;tudi&eacute; diff&eacute;rentes techniques spectroscopiques. Dans une solution riche k la hexacationic Zn (II) porphyrazine ligand ayant une fonctionnalit&eacute; de type cis-platin p&eacute;riph&eacute;rique modifie l&#39;&eacute;quilibre conformationnel G-quadruplexe de la s&eacute;quence t&eacute;lom&eacute;rique humaine 5&#39;-d[AGGG(TTAGGG)(3)] -3 &#39; et il entra&icirc;ne exclusivement vers une forme tr&egrave;s stable de la G4 parall&egrave;le dans le complexe de stoechiom&eacute;trie 2:1. Dans ce complexe par rapport &agrave; la G4 seul, on observe une augmentation de la temp&eacute;rature de fusion sup&eacute;rieure &agrave; 20 &deg; c. Au contraire liaison du ligand au G-quadruplexe de la m&ecirc;me s&eacute;quence t&eacute;lom&eacute;rique en solution riche na nettement influe sur la conformation pr&eacute;dominante panier ni conf&egrave;re une stabilit&eacute; thermique accrue &agrave; la structure du G4.

Tetra-2, 3-pyrazinoporphyrazines avec anneaux de pyridine externe joint en annexe. 10. A hydrosoluble bim&eacute;talliques (Zn(II)/Pt(II)) porphyrazine hexacation comme agent plurimodales potentiel pour le traitement du cancer : explorer le comportement comme ligand des structures d&#39;ADN G-quadruplexe t&eacute;lom&eacute;riques.

Il comportamento di un bimetallico solubile in acqua (Zn(II)/Pt(II)) porphyrazine hexacation come ligando di G-quadruplex (G4) strutture adottate da una sequenza di DNA umana telomerica &egrave; stata esaminata con differenti tecniche spettroscopiche. In soluzione ricca di K(+) hexacationic Zn(II) porphyrazine ligand recanti una funzionalit&agrave; periferica cis-platino-come cambia l&#39;equilibrio conformazionale G-quadruplex la sequenza telomerica umano 5&#39;-d[AGGG(TTAGGG)(3)] -3 &#39; e unit&agrave; esclusivamente verso una forma di G4 parallela molto stabile nel complesso con 2:1 stechiometria. In questo complesso rispetto al G4 da solo &egrave; osservato un aumento della temperatura di fusione superiore a 20 &deg; c. Al contrario associazione ligando a G-quadruplex della stessa sequenza telomerica in soluzione ricca Na(+) marcatamente influenza la conformazione del cestello predominante n&eacute; conferisce maggiore stabilit&agrave; termica della struttura G4.

Tetra-2,3-pyrazinoporphyrazines con anelli di piridina esternamente accodato. 10. Un idrosolubile bimetallici (Zn(II)/Pt(II)) porphyrazine hexacation come potenziale agente plurimodal per la terapia del cancro: esplorare il comportamento come ligando di telomeriche strutture di G-quadruplex di DNA.

El comportamiento de un bimet&aacute;lico soluble en agua (Zn(II)/Pt(II)) porphyrazine hexacation como ligando de G-quadruplex (G4) estructuras adoptadas por una secuencia de ADN telom&eacute;rica humana ha sido examinada con diferentes t&eacute;cnicas espectrosc&oacute;picas. En soluci&oacute;n de capacidad rica la hexacationic Zn(II) porphyrazine ligando con una funcionalidad de cis-platino-como perif&eacute;rica cambia el equilibrio conformacional quadruplex G de la 5&#39;-d[AGGG(TTAGGG)(3) de la secuencia telom&eacute;rica humana] -3 &#39; y unidades exclusivamente hacia una forma de G4 paralela muy estable en el complejo con la estequiometr&iacute;a de 2:1. Se observa un aumento de la temperatura de fusi&oacute;n de m&aacute;s de 20 &deg; C en este complejo en comparaci&oacute;n con el G4 solo. Por el contrario ligando a G-cu&aacute;druple de la misma secuencia telom&eacute;rica en soluci&oacute;n rica na marcado influye en la conformaci&oacute;n de la cesta predominante ni confiere mayor estabilidad t&eacute;rmica a la estructura del G4.

Tetra-2,3-pyrazinoporphyrazines con anillos de piridina externamente anexado. 10. Un soluble en agua bimet&aacute;lico (Zn(II)/Pt(II)) porphyrazine hexacation como agente plurimodal potencial para el tratamiento del c&aacute;ncer: explorando el comportamiento como ligando de estructuras de ADN G-quadruplex telom&eacute;ricas.

We report the synthesis and fibrillogenesis inhibiting activity of the new peptide derivatives 1-4, related to the pentapeptide Ac-LPFFD-NH(2) (iAÎ²5p), proposed by Soto and co-workers and widely recognized as one of the most active Î²-sheet breaker agents. The AÎ²(25-35) fragment of the parent full-length AÎ²(1-42) was used as fibrillogenesis model. The activity of peptide derivatives 1-4 was tested in vitro by thioflavin T binding assay, far UV CD spectroscopy, and scanning electron microscopy. Their ability to hinder the toxic effect of AÎ²(25-35) in vivo was studied by monitoring the viability of human SH-SY5Y neuroblastoma cells and the prevention of superoxide anion radical release from BV2 microglial cells. The results point to a favourable role in the fibrillogenesis inhibitory activity of the sulphonamide junction for compounds 1 and 2, containing an N,N-dimethyltaurine and a taurine amino-terminal moiety, respectively. Furthermore, compounds 1 and 2 show a significant protective effect on cell viability, rescuing the cells from the toxicity exerted by AÎ²(25-35) treatment.

Inhibition of amyloid peptide fragment AÎ²25-35 fibrillogenesis and toxicity by N-terminal Î²-amino acid-containing esapeptides: is taurine moiety essential for in vivo effects?

Nous rapportons la synth&egrave;se et FIBRILLOGENESE inhibant l&#39;activit&eacute; du nouveau peptide d&eacute;riv&eacute;s 1-4, concernant le pentapeptide Ac-LPFFD-NH(2) (iA&beta;5p), propos&eacute; par Soto et ses collaborateurs et largement reconnu comme un des agents plus actifs de disjoncteur feuillet &beta;. Le fragment A&beta;(25-35) du parent qu&#39;a&beta;(1-42) pleine longueur a &eacute;t&eacute; utilis&eacute;e comme mod&egrave;le de FIBRILLOGENESE. L&#39;activit&eacute; des d&eacute;riv&eacute;s de peptide 1-4 a &eacute;t&eacute; test&eacute;e in vitro par essai de liaison thioflavine T loin spectroscopie UV CD et microscopie &eacute;lectronique &agrave; balayage. Leur capacit&eacute; &agrave; emp&ecirc;cher l&#39;effet toxique des A&beta;(25-35) in vivo a &eacute;t&eacute; &eacute;tudi&eacute;e en surveillant la viabilit&eacute; des cellules de neuroblastome humains SH-SY5Y et la pr&eacute;vention de superoxyde anion radical acquit BV2 les cellules microgliales. Les r&eacute;sultats indiquent qu&#39;un r&ocirc;le favorable dans l&#39;activit&eacute; inhibitrice de le FIBRILLOGENESE de la jonction de sulfamide pour des compos&eacute;s 1 et 2, contenant une N, N-dimethyltaurine et une portion d&#39;amino-terminale taurine, respectivement. En outre, les compos&eacute;s 1 et 2 montrent un effet protecteur significatif sur la viabilit&eacute; cellulaire, sauvant les cellules de la toxicit&eacute; exerc&eacute;e par un traitement A&beta;(25-35).

L&#39;inhibition de la toxicit&eacute; par esapeptides de contenant de l&#39;acide &beta;-amin&eacute;s N-terminaux et de peptide b&ecirc;ta-amylo&iuml;de fragment AB25-35 FIBRILLOGENESE : portion taurine il est essentiel pour les effets in vivo ?

Riportiamo la sintesi e fibrillogenesis d&#39;inibizione attivit&agrave; del peptide nuovo derivati 1-4, imparentato con il pentapeptide Ac-LPFFD-NH(2) (iA&beta;5p), proposto da Soto e collaboratori e ampiamente riconosciuto come uno dei pi&ugrave; attivi agenti &beta;-foglio dell&#39;interruttore. Il frammento A&beta;(25-35) del padre che A&beta;(1-42) Full-length &egrave; stato utilizzato come modello di fibrillogenesis. L&#39;attivit&agrave; dei derivati del peptide 1-4 &egrave; stato testato in vitro da analisi obbligatoria thioflavin T lontano UV CD spettroscopia e microscopia elettronica a scansione. Loro capacit&agrave; di ostacolare l&#39;effetto tossico di A&beta;(25-35) in vivo &egrave; stato studiato monitorando la vitalit&agrave; delle cellule di neuroblastoma umano SH-SY5Y e la prevenzione di superossido anione radicale rilascio dalle cellule microgliali BV2. I risultati indicano un ruolo favorevole nell&#39;attivit&agrave; inibitoria della giunzione sulfonamide per composti fibrillogenesis 1 e 2, contenente una N, N-dimethyltaurine e un gruppo amminico-terminale taurina, rispettivamente. Inoltre, composti 1 e 2 mostrano un significativo effetto protettivo sulla vitalit&agrave; delle cellule, le cellule dalla tossicit&agrave; esercitata da A&beta;(25-35) trattamento di salvataggio.

Inibizione del peptide amiloide frammento 35 A&beta;25 fibrillogenesis e tossicit&agrave; da &beta;-amminici contenenti acido esapeptides di N-terminale: &egrave; essenziale per gli effetti in vivo moiety taurina?

Divulgamos la s&iacute;ntesis y fibrilog&eacute;nesis inhibiendo la actividad del p&eacute;ptido nuevo derivados 1-4, relacionada con el pentap&eacute;ptido Ac-LPFFD-NH(2) (iA&beta;5p), propuesto por Soto y compa&ntilde;eros de trabajo y ampliamente reconocido como uno de los agentes m&aacute;s activos de la &beta;-hoja interruptor. El fragmento A&beta;(25-35) de los padres que A&beta;(1-42) de larga duraci&oacute;n fue utilizado como modelo de fibrilog&eacute;nesis. La actividad de p&eacute;ptidos derivados 1-4 fue probada in vitro mediante ensayo de enlace tioflavina T lejos espectroscopia UV CD y microscop&iacute;a electr&oacute;nica de barrido. Su capacidad para impedir el efecto t&oacute;xico de A&beta;(25-35) in vivo se estudi&oacute; mediante el control de la viabilidad de las c&eacute;lulas de neuroblastoma SH-SY5Y humanas y la prevenci&oacute;n de la liberaci&oacute;n radical de ani&oacute;n de super&oacute;xido de BV2 las c&eacute;lulas microgliales. Los resultados apuntan a un papel favorable en la actividad inhibitoria de la fibrilog&eacute;nesis de la ensambladura de sulfamidas para compuestos 1 y 2, que contiene un N, N-dimethyltaurine y un grupo amino terminal taurino, respectivamente. Por otra parte, compuestos 1 y 2 muestran un efecto protector significativo en la viabilidad celular, rescatar a las c&eacute;lulas de la toxicidad ejercida por el tratamiento de A&beta;(25-35).

&iquest;Inhibici&oacute;n de p&eacute;ptido amiloide fragmento A&beta;25-35 fibrilog&eacute;nesis y toxicidad por esapeptides de que contiene &aacute;cido &beta;-amino N-terminal: es esencial para efectos in vivo la parte taurina?

The biological consequences of free radical production is the central subject of a very lively scientific debate, focusing on the estimation of the type and extent of damage, as well as the efficiency of the protective and repair systems. When studying free radical based chemical mechanisms, it is very important to establish biomimetic models, which allow the experiments to be performed in a simplified environment, but suitably designed to be in strict connection with cellular conditions. The biomimetic modeling approach has been coupled with physical organic chemistry methodologies and knowledge of free radical reactivity. Molecular basis of important processes have been identified, building up molecular libraries of products concerning unsaturated lipids, sulfur-containing proteins and nucleic acids, to be developed as biomarkers. Ongoing projects in our group deal with lipidomics, genomics and proteomics of free radical stress and some examples will be described.

Biomimetic models of radical stress and related biomarkers.

Les cons&eacute;quences biologiques de production de radicaux libres est le sujet central d&#39;un tr&egrave;s vif d&eacute;bat scientifique, en se concentrant sur l&#39;estimation du type et l&#39;&eacute;tendue des d&eacute;g&acirc;ts, ainsi que l&#39;efficacit&eacute; des syst&egrave;mes de protection et de r&eacute;paration. Lorsque l&#39;&eacute;tudiant radical libre selon les m&eacute;canismes chimiques, il est tr&egrave;s important d&#39;&eacute;tablir des mod&egrave;les biomim&eacute;tique, qui permettent les exp&eacute;riences &agrave; effectuer dans un environnement simplifi&eacute;, mais convenablement con&ccedil;us pour &ecirc;tre dans le cadre strict des conditions cellulaires. La biomim&eacute;tique, approche de mod&eacute;lisation s&#39;accompagne de m&eacute;thodes de chimie physique organique et connaissance de la r&eacute;activit&eacute; des radicaux libres. Bases mol&eacute;culaires des processus importants, accumulent des biblioth&egrave;ques mol&eacute;culaires de produits concernant les lipides insatur&eacute;s, prot&eacute;ines contenant du soufre et des acides nucl&eacute;iques, &agrave; d&eacute;velopper comme biomarqueurs ont &eacute;t&eacute; identifi&eacute;s. Projets en cours au sein du groupe traitent de la lipidomique, g&eacute;nomique et prot&eacute;omique de stress radicalaire et quelques exemples seront d&eacute;crites.

Mod&egrave;les biomim&eacute;tique du stress radicalaire et de biomarqueurs li&eacute;s.

Le conseguenze biologiche di produzione di radicali liberi &egrave; il soggetto centrale di un vivo dibattito scientifico, concentrandosi sulla stima del tipo e della entit&agrave; del danno, nonch&eacute; l&#39;efficienza dei sistemi di protezione e riparazione. Quando studiare radicale libero, basato su meccanismi chimici, &egrave; molto importante stabilire modelli biomimetici, che permettono gli esperimenti essere eseguito in un ambiente semplificato, ma opportunamente progettati per essere in stretta connessione con condizioni cellulari. Biomimetic approccio di modellazione &egrave; stato accoppiato con metodologie di chimica organica fisica e conoscenza della reattivit&agrave; di radicali liberi. Sono state identificate le basi molecolari di importanti processi, costruzione di librerie molecolari dei prodotti riguardanti i lipidi insaturi, contenenti zolfo proteine e acidi nucleici, per essere sviluppato come biomarcatori. Progetti in corso nel nostro gruppo affrontare lipidomica, genomica e proteomica di stress dei radicali liberi e verranno descritti alcuni esempi.

Modelli biomimetici di stress radicalico e biomarcatori correlati.

We investigated with spectroscopic techniques the noncovalent interaction of a bimetallic water-soluble (Zn(II)/Pt(II)) porphyrazine hexacation, [(PtCl(2))(CH(3))(6)LZn](6+), and its octacationic analogue [(CH(3))(8)LZn](8+), lacking the cis-platin-like functionality, with a 21-mer double strand (ds) 5'-d[GGG(TTAGGG)(3)]-3'/3'-d[CCC(AATCCC)(3)]-5', as model for B-DNA. Both hexacation and octacation tend to aggregate in water. The structure as well as the ground and excited-state electronic properties of the Zn(II)/Pt(II) hexacation [(PtCl(2))(CH(3))(6)LZn](6+) in water solution were investigated using density functional theory (DFT) and time-dependent DFT (TDDFT) methods. TDDFT calculations of the lowest excited states of [(PtCl(2))(CH(3))(6)LZn](6+) in water provided an accurate description of the Q-band spectral region. In particular, the calculated optical spectra were in agreement with the experimental ones, obtained in the presence of micelles favoring complete disruption of the aggregates. The model for dsDNA binding that emerges from the analysis of UV-vis absorption and time-resolved fluorescence data shows the presence of complexes of 1 dsDNA molecule with 1, 2, and 4 macrocycles. Comparing the results for the hexacation [(PtCl(2))(CH(3))(6)LZn](6+) with those for the [(CH(3))(8)LZn](8+)octacation, we observed a higher degree of monomerization for the [(PtCl(2))(CH(3))(6)LZn](6+) derivative.

Pyrazinoporphyrazines with externally appended pyridine rings. 13. Structure, UV-visible spectral features, and noncovalent interaction with DNA of a positively charged binuclear (Zn(II)/Pt(II)) macrocycle with multimodal anticancer potentialities.

Nous avons &eacute;tudi&eacute; avec des techniques spectroscopiques, l&#39;interaction non covalente d&#39;un bilame solubles dans l&#39;eau (Zn(II)/Pt(II)) porphyrazine hexacation, [(PtCl(2))(CH(3))(6)LZn](6+) et son analogue octacationic [(CH(3))(8)LZn](8+), d&eacute;pourvu de la fonctionnalit&eacute; de type cis-platine, avec un 5&#39;-d[GGG(TTAGGG)(3)]-3&#39;/3&#39;-d[CCC(AATCCC)(3) de double brin (ds) 21-mer] -5 &#39;, comme mod&egrave;le pour B-ADN. Les hexacation et octacation ont tendance &agrave; total dans l&#39;eau. La structure ainsi que les propri&eacute;t&eacute;s &eacute;lectroniques fondamental et &eacute;tat excit&eacute; de l&#39;hexacation de Zn(II)/Pt(II) [(PtCl(2))(CH(3))(6)LZn](6+) en solution aqueuse ont &eacute;t&eacute; &eacute;tudi&eacute;s &agrave; l&#39;aide de la th&eacute;orie fonctionnelle de la densit&eacute; (DFT) et m&eacute;thodes DFT (TDDFT) d&eacute;pendant du temps. Calculs de TDDFT des plus bas &eacute;tats excit&eacute;s de [(PtCl(2))(CH(3))(6)LZn](6+) dans l&#39;eau, a fourni une description pr&eacute;cise de la r&eacute;gion spectrale de Q-bande. En particulier, les spectres optiques calcul&eacute;s concordaient avec celles exp&eacute;rimentales, obtenues en pr&eacute;sence de micelles favorisant une d&eacute;sorganisation compl&egrave;te des agr&eacute;gats. Le mod&egrave;le d&#39;ADN double brin contraignant qui se d&eacute;gage de l&#39;analyse d&#39;absorption UV-vis et time-resolved fluorescence donn&eacute;es montrent la pr&eacute;sence de complexes de la mol&eacute;cule d&#39;ADN double 1 brin avec 1, 2 et 4 macrocycles. En comparant les r&eacute;sultats obtenus pour la hexacation [(PtCl(2))(CH(3))(6)LZn](6+) avec ceux de la [(CH(3)) (8) LZn](8+) octacation, nous avons observ&eacute; un degr&eacute; plus &eacute;lev&eacute; de monomerization pour le [(PtCl(2))(CH(3))(6)LZn](6+) d&eacute;riv&eacute;.

Pyrazinoporphyrazines avec anneaux de pyridine externe joint en annexe. 13. Structure, caract&eacute;ristiques spectrales UV-visible et interaction non covalente avec l&#39;ADN un charg&eacute;s positivement binucl&eacute;aire (Zn(II)/Pt(II)) macrocycle avec des potentialit&eacute;s anticanc&eacute;reuses multimodales.

Abbiamo studiato con tecniche spettroscopiche l&#39;interazione non covalente di una moneta bimetallica da solubile in acqua (Zn(II)/Pt(II)) porphyrazine hexacation, [(PtCl(2))(CH(3))(6)LZn](6+) e il suo analogo di octacationic [(CH(3))(8)LZn](8+), manca il cis-platino-come funzionalit&agrave;, con un 21-mer doppio filamento (ds) 5&#39;-d[GGG(TTAGGG)(3)]-3&#39;/3&#39;-d[CCC(AATCCC)(3)] -5 &#39;, come modello per B-DNA. Sia hexacation che octacation tendono ad aggregare in acqua. La struttura cos&igrave; come la terra e stato eccitato propriet&agrave; elettroniche del hexacation Zn(II)/Pt(II) [(PtCl(2))(CH(3))(6)LZn](6+) in soluzione acquosa furono studiate usando la teoria del funzionale della densit&agrave; (DFT) e metodi DFT (TDDFT) dipendente dal tempo. Calcoli TDDFT del pi&ugrave; basso eccitato gli Stati di [(PtCl(2))(CH(3))(6)LZn](6+) in acqua fornita un&#39;accurata descrizione della regione spettrale Q-band. In particolare, gli spettri ottici calcolati sono stati d&#39;accordo con quelli sperimentali, ottenuti in presenza di micelle favorendo la completa distruzione degli aggregati. Il modello per dsDNA vincolante che emerge dall&#39;analisi di assorbimento UV-vis e dati time-resolved di fluorescenza dimostra la presenza di complessi di 1 dsDNA molecola con 1, 2 e 4 macrocicli. Confrontando i risultati per il hexacation [(PtCl(2))(CH(3))(6)LZn](6+) con quelli per il [octacation](8+) (LZn CH(3)) (8), abbiamo osservato un maggiore grado di monomerization per il [(PtCl(2))(CH(3))(6)LZn](6+) derivato.

Pyrazinoporphyrazines con anelli di piridina esternamente accodato. 13. Struttura, caratteristiche spettrali UV-visibile e non covalente interazione con il DNA di un caricato positiva vacuolizzato (Zn(II)/Pt(II)) macrociclo con potenzialit&agrave; antitumorali multimodale.

Article	Year
Alpha-peptide/beta-sulfonamidopeptide hybrids: analogs of the chemotactic agent for-Met-Leu-Phe-OMe. Bioorganic & medicinal chemistry\| PubMed ID: 16356729	2006
Synthesis and activity of fibrillogenesis peptide inhibitors related to the 17-21 beta-amyloid sequence. European journal of medicinal chemistry\| PubMed ID: 18501995	2009
Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2. European journal of medicinal chemistry\| PubMed ID: 20692738	2010
Affinity of the anthracycline antitumor drugs Doxorubicin and Sabarubicin for human telomeric G-quadruplex structures. Physical chemistry chemical physics : PCCP\| PubMed ID: 21052579	2011
A cationic Zn(II) porphyrazine induces a stable parallel G-quadruplex conformation in human telomeric DNA. Organic & biomolecular chemistry\| PubMed ID: 21107490	2011
Complexes of the antitumoral drugs Doxorubicin and Sabarubicin with telomeric G-quadruplex in basket conformation: ground and excited state properties. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology\| PubMed ID: 21655621	2011
Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 10. A water-soluble bimetallic (Zn(II)/Pt(II)) porphyrazine hexacation as potential plurimodal agent for cancer thera... Inorganic chemistry\| PubMed ID: 21770396	2011
Inhibition of amyloid peptide fragment AÎ²25-35 fibrillogenesis and toxicity by N-terminal Î²-amino acid-containing esapeptides: is taurine moiety essential for in vivo effects? Chemical biology & drug design\| PubMed ID: 21995332	2012
Biomimetic models of radical stress and related biomarkers. Chimia\| PubMed ID: 22871276	2012
Pyrazinoporphyrazines with externally appended pyridine rings. 13. Structure, UV-visible spectral features, and noncovalent interaction with DNA of a positively charged binuclear (Zn(II)/Pt(... Inorganic chemistry\| PubMed ID: 23244699	2013

Annalisa Masi

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