Abstract
For several drug leads obtained by tethering weak binding ligands, the dissociation constant is smaller than the product of those of the individual fragments by a factor named the linking coefficient, E. This favorable contribution is attributed to the entropic gain that is realized when two weak binding ligands are tethered. Here we show a case study where the linking coefficient is strikingly small (E = 2.1 x 10(-3) M(-1)) and its totally entropic nature is demonstrated.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Calorimetry
-
Catalytic Domain
-
Crystallography, X-Ray
-
Drug Design*
-
Entropy*
-
Hydroxamic Acids / chemistry*
-
Ligands
-
Magnetic Resonance Spectroscopy
-
Matrix Metalloproteinase 12 / chemistry*
-
Matrix Metalloproteinase Inhibitors*
-
Models, Molecular
-
Protein Binding
-
Sulfonamides / chemistry*
Substances
-
Hydroxamic Acids
-
Ligands
-
Matrix Metalloproteinase Inhibitors
-
Sulfonamides
-
acetohydroxamic acid
-
Matrix Metalloproteinase 12