Peptide fibrils as monomer storage of the covalent HIV-1 integrase inhibitor

Koushik Chandra; Priyadip Das; Norman Metanis; Assaf Friedler; Meital Reches

doi:10.1002/psc.2959

Peptide fibrils as monomer storage of the covalent HIV-1 integrase inhibitor

Koushik Chandra
, Priyadip Das
, Norman Metanis
, Assaf Friedler
, Meital Reches^*

^*Corresponding author for this work

Institute of Chemistry

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

2 Scopus citations

Abstract

We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361–370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents.

Original language	English
Pages (from-to)	117-121
Number of pages	5
Journal	Journal of Peptide Science
Volume	23
Issue number	2
DOIs	https://doi.org/10.1002/psc.2959
State	Published - 1 Feb 2017

Bibliographical note

Publisher Copyright:
Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

HIV-1 integrase
covalent inhibition
fibrillization
peptides
succinimide

Access to Document

10.1002/psc.2959

Cite this

@article{2548f95aae2142809be76e8053d6084d,

title = "Peptide fibrils as monomer storage of the covalent HIV-1 integrase inhibitor",

abstract = "We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361–370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents.",

keywords = "HIV-1 integrase, covalent inhibition, fibrillization, peptides, succinimide",

author = "Koushik Chandra and Priyadip Das and Norman Metanis and Assaf Friedler and Meital Reches",

note = "Publisher Copyright: Copyright {\textcopyright} 2017 European Peptide Society and John Wiley \& Sons, Ltd.",

year = "2017",

month = feb,

day = "1",

doi = "10.1002/psc.2959",

language = "אנגלית",

volume = "23",

pages = "117--121",

journal = "Journal of Peptide Science",

issn = "1075-2617",

publisher = "John Wiley and Sons Ltd",

number = "2",

}

TY - JOUR

T1 - Peptide fibrils as monomer storage of the covalent HIV-1 integrase inhibitor

AU - Chandra, Koushik

AU - Das, Priyadip

AU - Metanis, Norman

AU - Friedler, Assaf

AU - Reches, Meital

PY - 2017/2/1

Y1 - 2017/2/1

N2 - We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361–370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents.

AB - We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361–370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents.

KW - HIV-1 integrase

KW - covalent inhibition

KW - fibrillization

KW - peptides

KW - succinimide

UR - https://www.scopus.com/pages/publications/85013105636

U2 - 10.1002/psc.2959

DO - 10.1002/psc.2959

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 28070909

AN - SCOPUS:85013105636

SN - 1075-2617

VL - 23

SP - 117

EP - 121

JO - Journal of Peptide Science

JF - Journal of Peptide Science

IS - 2

ER -

Peptide fibrils as monomer storage of the covalent HIV-1 integrase inhibitor

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this