Irreversible Binding
Irreversible Binding - Related Videos
03:50
Irreversible Electroporation: A Technique for Ablating Pancreatic Tumor in Mouse
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2023
This video describes the procedure for performing irreversible electroporation (IRE) for non-thermal ablation of pancreatic tumors in mice. Both subcutaneous (SQ) and orthotopic tumors can be successfully treated with IRE in a highly controlled setting, facilitating various studies post-procedure.
14:05
A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction
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Cited by 47 •
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The murine model of irreversible unilateral ureteric obstruction (UUO) is presented together with the model of reversible UUO in which the ureteric obstruction is relieved by anastomosis of the severed ureter into the bladder. These models enable the study of renal inflammation and scarring as well as tissue remodeling.
01:14
Reversible and Irreversible Processes
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2023
The thermodynamic processes can be classified into reversible and irreversible processes. The processes that can be restored to their initial state are called reversible processes. It is only possible if the process is in quasi-static equilibrium, i.e., it takes place in infinitesimally small steps, and the system remains at equilibrium However, these are ideal processes and do not occur naturally. An ideal system undergoing a reversible process is always in thermodynamic equilibrium within...
02:18
The Equilibrium Binding Constant and Binding Strength
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2020
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium: where P and L are the unbound protein and ligand, respectively, and PL is the protein-ligand complex. As the amount of bound ligand is also related to the rate of ligand binding, experiments can also determine Kb by examining the rates of protein-ligand association (kon) and dissociation (koff) using the following ratio: Thus,...
06:17
Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
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2025
The quantitative irreversible tethering (qIT) assay is a fluorescence-based method of identifying covalent fragments that selectively engage with a target protein. Here, a detailed protocol is outlined to describe the qIT assay, with example results included.
FAQs
Persistence arises from the stability of the drug-target connection, not simply from high drug concentration. Noncovalent interactions can dissociate, whereas covalent attachment to a target residue prevents readily reversible separation. Consequently, removing unbound drug may not immediately restore activity. This distinction helps pharmacologists interpret why target inhibition or receptor inactivation can outlast measurable drug exposure.
Reactive drug groups determine which biological targets can be modified because they must encounter suitable amino acid residues on enzymes or receptors. The resulting chemical modification can block enzyme function or inactivate receptor activity. Thus, the location and reactivity of the drug group influence pharmacological selectivity, while unwanted reactions with other proteins raise concerns about off-target modification.
Drug half-life and effect duration can diverge with irreversible binding. Plasma drug levels may fall as unbound compound is cleared, yet the modified target can remain inactive. Functional recovery therefore depends largely on synthesis of new target molecules rather than on redistribution or elimination of the original drug. This relationship is important when interpreting prolonged responses after brief exposure.
A useful pharmacological comparison is to examine target function after unbound drug has been cleared. If inhibition or receptor inactivation persists, the result is consistent with a stable drug-target interaction rather than an effect maintained only by free compound. This interpretation links exposure measurements with recovery observations and helps characterize the duration of action.
Irreversible binding is especially valuable when a sustained pharmacological effect is desired. Drug design can exploit reactive groups to create long-acting enzyme inhibitors, and the same principle can produce prolonged receptor inactivation. These applications show why persistence may be therapeutically useful: activity can remain suppressed beyond the compound’s plasma half-life, reducing dependence on continued circulating drug.
The same persistence that supports long-lasting treatment can become harmful if a reactive drug group modifies unintended proteins. Because unwanted protein modification may continue to influence function after free drug is gone, pharmacologists must consider both the intended target and possible off-target interactions when evaluating an irreversible compound’s safety and therapeutic usefulness.