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.
Entropic contribution to the linking coefficient in fragment based drug design: a case study / V.Borsi; V.Calderone; M.Fragai; C.Luchinat; N.Sarti. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 27:(2010), pp. 4285-4289. [10.1021/jm901723z]
Entropic contribution to the linking coefficient in fragment based drug design: a case study.
BORSI, VALENTINA;CALDERONE, VITO;FRAGAI, MARCO;LUCHINAT, CLAUDIO;SARTI, NIKO
2010
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.
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