Ligand interactions kinetics

Mittag T, Schaffhausen B, Gunther UL. Direct observation of 117. protein-ligand interaction kinetics. Biochemistry 2003 42 11128-11136. 

Sanders (83) constructed a supramolecular assembly of heterometal-lic porphyrins held together by different types of metal-ligand interaction. The team exploited the different kinetic and thermodynamic properties of the pyridine-zinc, carboxylate-tin, and pyridine-... 

Lortat-Jacob, H., Chouin, E., Cusack, S., and van Raaij, M.J. (2001). Kinetic analysis of adenovirus fiber binding to its receptor reveals an avidity mechanism for trimeric receptor-ligand interactions./. Biol. Chem. 276, 9009-9015. 

Several kinetic parameters can be measured on different experimental systems to account for the interaction of a compound with CYPs. For example when studying the metabolic stability of a compound, it could be measured in a recombinant CYP system, in human liver microsomes, in hepatocytes and so on. Each system increases in biological complexity. Although in the recombinant CYP system only the cytochrome under consideration is studied, in the case of the human liver microsomes, there is a pool of enzyme present that includes several CYPs, and finally in the hepatocyte cell system, metabolizing enzymes play an important role in the metabolic compound stability. In addition, transport systems are also present that could involve recirculation or other transport phenomena. The more complex the experimental system, the more difficult it is to extract information on the protein/ligand interaction, albeit it is closer to the in vivo real situation and therefore to the mechanism that is actually working in the body. 

Receptor-Ligand Interactions Simple Kinetic Theory.264... 

The information contained in karma s knowledge bases is based upon quantitative structure-activity relationships (QSAR), kinetic data, and structural chemistry. The combination of QSAR and kinetic data allows for the study of enzyme-ligand interactions. The Hansch approach to QSAR, based on a set of congeners, states ... 

Also, very slow dissociation kinetics can contribute to slow clearing of a drug, which can be problematic in the event of adverse reactions such as an undesired allergic response. Therefore, methods to accurately determine the dissociation kinetics for protein-ligand interactions are of great value to the drug discovery process. 

Substituting these expressions into the equations above yields a new expression that enables the interaction kinetics to be readily modeled for single-site, reversible binding between a protein and a single ligand ... 

In order to elicit their effect, drug molecules must be bound to the cells of the effector organ. Binding commonly occurs at specific cell structures, namely, the receptors. The analysis of drug binding to receptors aims to determine the affinity of ligands, the kinetics of interaction, and the characteristics of the binding site itself. 

Stereochemical probes of the specificity of substrates, products, and effectors in enzyme-catalyzed reactions, receptor-ligand interactions, nucleic acid-ligand interactions, etc. Most chirality probe studies attempt to address the stereospecificity of the substrates or ligands or even allosteric effectors. However, upon use of specific kinetic probes, isotopic labeling of achiral centers, chronfium-or cobalt-nucleotide complexes, etc., other stereospecific characteristics can be identified, aU of which will assist in the delineation of the kinetic mechanism as well as the active-site topology. A few examples of chirality probes include ... 

X 10 M s . This illustrates the degree to which electrostatic interactions can change a reaction from a diffusion-limited process to one that involves other types of protein-ligand interactions. See Chemical Kinetics Diffusion-Limited Reaction... 

R.E. London, S.A. Gabel, F-19 NMR-studies of fluorobenzeneboronic acids. 1. Interaction kinetics with biologically significant ligands, J. Am. Chem. Soc. 116 (1994) 2562-2569. 

The isolation of both specific and nonspecific binding proteins on affinity matrices bearing bioactive compounds hinders the identification of drug cellular targets. While solid-phase elution or the competition methods are conventionally used to distinguish between specific and nonspecific receptor-ligand interactions, these approaches are often severely restricted by low ligand solubility and/or slow kinetic dissociation (8). This low solubility of these compounds are not uncommon, since the hydrophobic properties of these compounds are often vital for their bioactivity and/or membrane permeability. 

---