Protein-binding affinity

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

A crystallographic study of drug binding to HSA provides a valuable resource for structure-based design efforts to modify protein binding affinity of... 

Lipooligosaccharide (LOS) bacterial, 25 498 Lipophilic amphiphiles, 24 154-155 Lipophilic interaction dominated substrate recognition, 16 783-786 Lipophilic moieties, 8 706t Lipopolysaccharides (LPS), 4 706 11 47 BPI protein ability to neutralize, 18 257 peptide and protein binding affinity to, 18 256... 

For example, our preliminary MALDI MS studies employed a somewhat unconventional sample preparation approach in which the protein deposition step preceded the matrix deposition step. (In the conventional approach, the protein is co-deposited with the MALDI matrix solution.). .. Thus, in the first/next/colleclively group of experiments, we will explore different sample preparation methods to determine if other protocols also lead to an inverse relationship between surface-protein binding affinity and the MALDI ion signal. 

These studies will be followed with experiments that examine the influence of the matrix solvent on the inverse surface-protein binding affinity/MALDI ion signal relationship. 

Gleeson, M.P. (2007) Plasma protein binding affinity and its relationship to molecular structure an in-silico analysis. Journal of Medicinal Chemistry, 50, 101-112. 

Saiakhov, R.D., Stefan, L.R., and Klopman, G., Multiple computer-automated structure evaluation model of the plasma protein binding affinity of diverse drugs, Perspect. Drug Discovery Design 19, 133-155, 2000. 

Appropriate experiments have shown that the inhibitory ET effects are not a consequence of changes in protein protein binding affinity, in Fd redox potential or in the 3-D structures of the mutant proteins [49]. However, nonconservative mutations at the critical positions do have significant effects on a number of protein... 

Gartenberg, M. R. Crothers, D. M. (1988). DNA sequence determinants of CAP-induced bending and protein binding affinity. Nature 333, 824-829. 

In neonates drugs such as various penicillins, pheno-barbital, phenytoin, and theophylline have lower protein-binding affinity than in adults. This may increase the concentration of free or pharmacological active drug in neonates, and may also change the apparent volume of distribution. Thus, neonates may require different doses on a mg/kg basis compared to that for adults for these drugs to achieve appropriate therapeutic serum concentrations. 

Metabolism of ASOs occurs primarily through degradation by exonucleases and endonucleases. Degradation products have lower protein binding affinity and higher solubility, facilitating their excretion in urine and exhaled air [65, 121, 123-125]. 

Audie, J., Scarlata, S. A novel empirical free energy function that explains and predicts protein-protein binding affinities. Biophys. Chem. 2007,129,198-211. 

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