Stoichiometry and physical chemistry of promiscuous aggregate-based inhibitors.

ABSTRACT: Many false positives in early drug discovery owe to nonspecific inhibition by colloid-like aggregates of organic molecules. Despite their prevalence, little is known about aggregate concentration, structure, or dynamic equilibrium; the binding mechanism, stoichiometry with, and affinity for enzymes remain uncertain. To investigate the elementary question of concentration, we counted aggregate particles using flow cytometry. For seven aggregate-forming molecules, aggregates were not observed until the concentration of monomer crossed a threshold, indicating a "critical aggregation concentration" (CAC). Above the CAC, aggregate count increased linearly with added organic material, while the particles dispersed when diluted below the CAC. The concentration of monomeric organic molecule is con

SUBMITTER: Coan KE 

PROVIDER: S-EPMC2627561 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature