Covalent Inhibition of HIV-1 Integrase by N-Succinimidyl Peptides

Koushik Chandra; Priyadip Das; Samarasimhareddy Mamidi; Mattan Hurevich; Anat Iosub-Amir; Norman Metanis; Meital Reches; Assaf Friedler

doi:10.1002/cmdc.201600190

Covalent Inhibition of HIV-1 Integrase by N-Succinimidyl Peptides

Koushik Chandra, Priyadip Das, Samarasimhareddy Mamidi, Mattan Hurevich, Anat Iosub-Amir, Norman Metanis, Meital Reches, Assaf Friedler

Institute of Chemistry

The Hebrew University of Jerusalem

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

Abstract

We present a new approach for the covalent inhibition of HIV-1 integrase (IN) by an LEDGF/p75-derived peptide modified with an N-terminal succinimide group. The covalent inhibition is mediated by direct binding of the succinimide to the amine group of a lysine residue in IN. The peptide serves as a specific recognition sequence for the target protein, while the succinimide serves as the binding moiety. The combination of a readily synthesizable peptide precursor with easy and efficient binding to the target protein makes this approach a promising new strategy for designing lead compounds.

Original language	English
Pages (from-to)	1987-1994
Number of pages	8
Journal	ChemMedChem
DOIs	https://doi.org/10.1002/cmdc.201600190
State	Published - 2016

Keywords

HIV-1 integrase
covalent inhibitors
peptides
succinimide

All Science Journal Classification (ASJC) codes

Drug Discovery
General Pharmacology, Toxicology and Pharmaceutics
Molecular Medicine
Biochemistry
Pharmacology
Organic Chemistry

UN SDGs

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

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10.1002/cmdc.201600190

Cite this

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title = "Covalent Inhibition of HIV-1 Integrase by N-Succinimidyl Peptides",

abstract = "We present a new approach for the covalent inhibition of HIV-1 integrase (IN) by an LEDGF/p75-derived peptide modified with an N-terminal succinimide group. The covalent inhibition is mediated by direct binding of the succinimide to the amine group of a lysine residue in IN. The peptide serves as a specific recognition sequence for the target protein, while the succinimide serves as the binding moiety. The combination of a readily synthesizable peptide precursor with easy and efficient binding to the target protein makes this approach a promising new strategy for designing lead compounds.",

keywords = "HIV-1 integrase, covalent inhibitors, peptides, succinimide",

author = "Koushik Chandra and Priyadip Das and Samarasimhareddy Mamidi and Mattan Hurevich and Anat Iosub-Amir and Norman Metanis and Meital Reches and Assaf Friedler",

note = "Publisher Copyright: {\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2016",

doi = "10.1002/cmdc.201600190",

language = "الإنجليزيّة",

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journal = "ChemMedChem",

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T1 - Covalent Inhibition of HIV-1 Integrase by N-Succinimidyl Peptides

AU - Chandra, Koushik

AU - Das, Priyadip

AU - Mamidi, Samarasimhareddy

AU - Hurevich, Mattan

AU - Iosub-Amir, Anat

AU - Metanis, Norman

AU - Reches, Meital

AU - Friedler, Assaf

PY - 2016

Y1 - 2016

N2 - We present a new approach for the covalent inhibition of HIV-1 integrase (IN) by an LEDGF/p75-derived peptide modified with an N-terminal succinimide group. The covalent inhibition is mediated by direct binding of the succinimide to the amine group of a lysine residue in IN. The peptide serves as a specific recognition sequence for the target protein, while the succinimide serves as the binding moiety. The combination of a readily synthesizable peptide precursor with easy and efficient binding to the target protein makes this approach a promising new strategy for designing lead compounds.

AB - We present a new approach for the covalent inhibition of HIV-1 integrase (IN) by an LEDGF/p75-derived peptide modified with an N-terminal succinimide group. The covalent inhibition is mediated by direct binding of the succinimide to the amine group of a lysine residue in IN. The peptide serves as a specific recognition sequence for the target protein, while the succinimide serves as the binding moiety. The combination of a readily synthesizable peptide precursor with easy and efficient binding to the target protein makes this approach a promising new strategy for designing lead compounds.

KW - HIV-1 integrase

KW - covalent inhibitors

KW - peptides

KW - succinimide

UR - http://www.scopus.com/inward/record.url?scp=84987962143&partnerID=8YFLogxK

U2 - 10.1002/cmdc.201600190

DO - 10.1002/cmdc.201600190

M3 - مقالة

C2 - 27331774

SN - 1860-7179

SP - 1987

EP - 1994

JO - ChemMedChem

JF - ChemMedChem

ER -

Covalent Inhibition of HIV-1 Integrase by N-Succinimidyl Peptides

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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