Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm
| Autor: | Salim Joubran, Laurence Briant-Longuet, Noam S. Freeman, Mattan Hurevich, Martine Bardy, Amnon Hoffman, Christian Devaux, Elena Britan-Rosich, Chaim Gilon, Avi Swed, Moshe Kotler, Shira Cohen |
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| Přispěvatelé: | Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Drug Macrocyclic Compounds Anti-HIV Agents Stereochemistry media_common.quotation_subject Clinical Biochemistry Administration Oral Pharmaceutical Science HIV Envelope Protein gp120 01 natural sciences Biochemistry Chemical synthesis 03 medical and health sciences chemistry.chemical_compound In vivo Drug Discovery Peptide synthesis Animals Humans HATU Rats Wistar Molecular Biology 030304 developmental biology media_common chemistry.chemical_classification 0303 health sciences Binding Sites 010405 organic chemistry Organic Chemistry In vitro Cyclic peptide Rats 0104 chemical sciences 3. Good health chemistry Drug Design CD4 Antigens [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology HIV-1 Molecular Medicine Lead compound Protein Binding |
| Zdroj: | Bioorganic and Medicinal Chemistry Bioorganic and Medicinal Chemistry, Elsevier, 2010, 18 (15), pp.5754-5761. ⟨10.1016/j.bmc.2010.04.053⟩ |
| ISSN: | 0968-0896 1464-3391 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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