Stereoselective binding of an enantiomeric pair of stromelysin-1 inhibitors caused by conformational entropy factors

M H Parker; D F Ortwine; P M O'Brien; E A Lunney; C A Banotai; W T Mueller; P McConnell; C G Brouillette

doi:10.1016/s0960-894x(00)00495-9

Stereoselective binding of an enantiomeric pair of stromelysin-1 inhibitors caused by conformational entropy factors

Bioorg Med Chem Lett. 2000 Nov 6;10(21):2427-30. doi: 10.1016/s0960-894x(00)00495-9.

Authors

M H Parker¹, D F Ortwine, P M O'Brien, E A Lunney, C A Banotai, W T Mueller, P McConnell, C G Brouillette

Affiliation

¹ University of Alabama at Birmingham, 35294, USA. [email protected]

PMID: 11078193
DOI: 10.1016/s0960-894x(00)00495-9

Abstract

Isothermal titration calorimetry was used to analyze the binding of an enantiomeric pair of inhibitors to the stromelysin-1 catalytic domain. Differences in binding affinity are attributable to different conformational entropy penalties suffered upon binding. Two possible explanations for these differences are proposed.

MeSH terms

Calorimetry / methods
Catalytic Domain
Humans
Hydroxamic Acids / chemistry*
Hydroxamic Acids / metabolism*
Matrix Metalloproteinase 3 / metabolism
Matrix Metalloproteinase Inhibitors*
Molecular Conformation
Molecular Structure
Oligopeptides / chemistry*
Oligopeptides / metabolism*
Protease Inhibitors / chemistry*
Protease Inhibitors / metabolism*
Protein Binding
Stereoisomerism
Thermodynamics

Substances

(R)-2-(4'-bromo-biphenyl-4-sulfonyl-amino)-3-methyl-butyric acid
Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Oligopeptides
Protease Inhibitors
Matrix Metalloproteinase 3