Introduction of Intrinsic Kinetics of Protein-Ligand Interactions and Their Implications for Drug Design.

LinkuvienÄ— V, Talibov VO, Danielson UH, Matulis D

J. Med. Chem. 61 (6) 2292-2302 [2018-03-22; online 2018-03-02]

Structure-kinetic relationship analyses and identification of dominating interactions for optimization of lead compounds should ideally be based on intrinsic rate constants instead of the more easily accessible observed kinetic constants, which also account for binding-linked reactions. The intrinsic rate constants for sulfonamide inhibitors and pharmacologically relevant isoforms of carbonic anhydrase were determined by a novel surface plasmon resonance (SPR) biosensor-based approach, using chemodynamic analysis of binding-linked pH-dependent effects. The observed association rates ( k

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PubMed 29466001

DOI 10.1021/acs.jmedchem.7b01408

Crossref 10.1021/acs.jmedchem.7b01408