Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Bioorganic and Medicinal Chemistry Année : 2010

Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm.

Mattan Hurevich
  • Fonction : Auteur
Avi Swed
  • Fonction : Auteur
Salim Joubran
  • Fonction : Auteur
Shira Cohen
  • Fonction : Auteur
Noam S Freeman
  • Fonction : Auteur
Elena Britan-Rosich
  • Fonction : Auteur
Laurence Briant
Moshe Kotler
  • Fonction : Auteur
Amnon Hoffman
  • Fonction : Auteur
Chaim Gilon
  • Fonction : Auteur

Résumé

Rational conversion of noncontinuous active regions of proteins into a small orally bioavailable molecule is crucial for the discovery of new drugs based on inhibition of protein-protein interactions. We developed a method that utilizes backbone cyclization as an intermediate step for conversion of the CD4 noncontinuous active region into small macrocyclic molecules. We demonstrate that this method is feasible by preparing small inhibitor for human immunodeficiency virus infection. The lead compound, CG-1, proved orally available in the rat model.

Domaines

Virologie

Dates et versions

hal-00505767 , version 1 (26-07-2010)

Identifiants

Citer

Mattan Hurevich, Avi Swed, Salim Joubran, Shira Cohen, Noam S Freeman, et al.. Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm.. Bioorganic and Medicinal Chemistry, 2010, 18 (15), pp.5754-5761. ⟨10.1016/j.bmc.2010.04.053⟩. ⟨hal-00505767⟩
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