an-efficient-method-for-synthesis-peptoids-with-mixed-lysine

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this ...

Durham University

Peptoids, a class of peptide mimetics, have emerged as promising anti-infective agents against a range of bacterial infections. Herein we present the first study of the antiparasitic and specifically the anti-leishmanial properties of linear peptoids. Peptoids were identified as having promising activity against Leishmania mexicana axenic amastigotes, a causative agent of cutaneous leishmaniasis.

Investigating the anti-leishmanial effects of linear peptoids.

Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that the mammalian pathogenic amastigote form of L. mexicana, a causative agent of cutaneous leishmaniasis, is resistant to the amphibian-derived temporin family of AMPs when compared to the insect stage promastigote form. The mode of resistance is unknown, however the insect and mammalian stages of Leishmania possess radically different cell surface coats, with amastigotes displaying low (or zero) quantities of lipophosphoglycan (LPG) and proteophosphoglycan (PPG), macromolecules which form thick a glycocalyx in promastigotes. It has been predicted that negatively charged LPG and PPG influence the sensitivity/resistance of promastigote forms to cationic temporins. Using LPG and PPG mutant L. mexicana, and an extended range of temporins, in this study we demonstrated that whilst LPG has little role, PPG is a major factor in promastigote sensitivity to the temporin family of AMPs, possibly due to the conferred anionic charge. Therefore, the lack of PPG seen on the surface of pathogenic amastigote L. mexicana may be implicated in their resistance to these peptides.

The role of phosphoglycans in the susceptibility of Leishmania mexicana to the temporin family of anti-microbial peptides.

Tris[bis(triphenylphosphoranylidene)ammonium] pyrophosphate (PPN pyrophosphate) was used in the SN2 displacements of the tosylate ion from 5'-tosylnucleosides to afford nucleoside-5'-diphosphates. Selective precipitation permitted the direct isolation of nucleoside-5'-diphosphates from crude reaction mixtures.

Article	Year
Investigating the anti-leishmanial effects of linear peptoids. ChemMedChem\| PubMed ID: 25512204	2015
The role of phosphoglycans in the susceptibility of Leishmania mexicana to the temporin family of anti-microbial peptides. Molecules (Basel, Switzerland)\| PubMed ID: 25668079	2015
A procedure for the preparation and isolation of nucleoside-5'-diphosphates. Beilstein journal of organic chemistry\| PubMed ID: 25977720	2015

Hannah L. Bolt

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