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; Avi Swed; Salim Joubran; Shira Cohen; Noam S. Freeman; Elena Britan-Rosich; Laurence Briant-Longuet; Martine Bardy; Christian Devaux; Moshe Kotler; Amnon Hoffman; Chaim Gilon

doi:10.1016/j.bmc.2010.04.053

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^*
, Avi Swed
, Salim Joubran
, Shira Cohen
, Noam S. Freeman
, Elena Britan-Rosich
, Laurence Briant-Longuet
, Martine Bardy
, Christian Devaux
, Moshe Kotler
, Amnon Hoffman
, Chaim Gilon

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	5754-5761
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	15
DOIs	https://doi.org/10.1016/j.bmc.2010.04.053
State	Published - 1 Aug 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Backbone cyclization
Drug design
HIV-1
Macrocycles
Proteomics

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10.1016/j.bmc.2010.04.053

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Hurevich, M., Swed, A., Joubran, S., Cohen, S., Freeman, N. S., Britan-Rosich, E., Briant-Longuet, L., Bardy, M., Devaux, C., Kotler, M., Hoffman, A., & Gilon, C. (2010). 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, 18(15), 5754-5761. https://doi.org/10.1016/j.bmc.2010.04.053

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abstract = "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.",

keywords = "Backbone cyclization, Drug design, HIV-1, Macrocycles, Proteomics",

author = "Mattan Hurevich and Avi Swed and Salim Joubran and Shira Cohen and Freeman, \{Noam S.\} and Elena Britan-Rosich and Laurence Briant-Longuet and Martine Bardy and Christian Devaux and Moshe Kotler and Amnon Hoffman and Chaim Gilon",

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Hurevich, M, Swed, A, Joubran, S, Cohen, S, Freeman, NS, Britan-Rosich, E, Briant-Longuet, L, Bardy, M, Devaux, C, Kotler, M , Hoffman, A & Gilon, C 2010, '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, vol. 18, no. 15, pp. 5754-5761. https://doi.org/10.1016/j.bmc.2010.04.053

TY - JOUR

T1 - Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule

T2 - The HIV-1 CD4:gp120 paradigm

AU - Hurevich, Mattan

AU - Swed, Avi

AU - Joubran, Salim

AU - Cohen, Shira

AU - Freeman, Noam S.

AU - Britan-Rosich, Elena

AU - Briant-Longuet, Laurence

AU - Bardy, Martine

AU - Devaux, Christian

AU - Kotler, Moshe

AU - Hoffman, Amnon

AU - Gilon, Chaim

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

KW - Backbone cyclization

KW - Drug design

KW - HIV-1

KW - Macrocycles

KW - Proteomics

UR - https://www.scopus.com/pages/publications/77955422125

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AN - SCOPUS:77955422125

SN - 0968-0896

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SP - 5754

EP - 5761

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 15

ER -

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

Abstract

UN SDGs

Keywords

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