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^*

^*Corresponding author for this work

Institute of Chemistry

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

4 Scopus citations

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

Bibliographical note

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

HIV-1 integrase
covalent inhibitors
peptides
succinimide

UN SDGs

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

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10.1002/cmdc.201600190

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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.",

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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

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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.

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

Abstract

Bibliographical note

Keywords

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