Evaluations of substrate specificity and inhibition at PR/p3 cleavage site of HTLV-1 protease

Hiromi Naka; Kenta Teruya; Jeong Kyu Bang; Saburo Aimoto; Tadashi Tatsumi; Hiroyuki Konno; Kazuto Nosaka; Kenichi Akaji

doi:10.1016/j.bmcl.2006.04.056

Evaluations of substrate specificity and inhibition at PR/p3 cleavage site of HTLV-1 protease

Hiromi Naka, Kenta Teruya, Jeong Kyu Bang, Saburo Aimoto, Tadashi Tatsumi, Hiroyuki Konno, Kazuto Nosaka, Kenichi Akaji

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

10 Citations (Scopus)

Abstract

Core sequences necessary for substrate recognition and its inhibition at the PR/p3 site of HTLV-1 protease were clarified for the first time. From the cleavage rates of peptides containing a part of the PR/p3 site, a heptapeptide was found to be the minimal sequence required for substrate recognition. The use of synthetic inhibitors containing hydroxyethylamine dipeptide isostere indicated that a tetrapeptide sequence was necessary to achieve potent inhibition.

Original language	English
Pages (from-to)	3761-3764
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2006.04.056
Publication status	Published - 2006 Jul 15
Externally published	Yes

Keywords

HTLV-1 protease
Hydroxyethylamine dipeptide isostere
Inhibitor
Substrate specificity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2006.04.056

Cite this

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title = "Evaluations of substrate specificity and inhibition at PR/p3 cleavage site of HTLV-1 protease",

abstract = "Core sequences necessary for substrate recognition and its inhibition at the PR/p3 site of HTLV-1 protease were clarified for the first time. From the cleavage rates of peptides containing a part of the PR/p3 site, a heptapeptide was found to be the minimal sequence required for substrate recognition. The use of synthetic inhibitors containing hydroxyethylamine dipeptide isostere indicated that a tetrapeptide sequence was necessary to achieve potent inhibition.",

keywords = "HTLV-1 protease, Hydroxyethylamine dipeptide isostere, Inhibitor, Substrate specificity",

author = "Hiromi Naka and Kenta Teruya and Bang, {Jeong Kyu} and Saburo Aimoto and Tadashi Tatsumi and Hiroyuki Konno and Kazuto Nosaka and Kenichi Akaji",

note = "Funding Information: This research was supported in part by a grant from Mitsubishi Pharma Research Foundation, and a grant from Japan Leukemia Research Fund. ",

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language = "English",

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T1 - Evaluations of substrate specificity and inhibition at PR/p3 cleavage site of HTLV-1 protease

AU - Naka, Hiromi

AU - Teruya, Kenta

AU - Bang, Jeong Kyu

AU - Aimoto, Saburo

AU - Tatsumi, Tadashi

AU - Konno, Hiroyuki

AU - Nosaka, Kazuto

AU - Akaji, Kenichi

N1 - Funding Information: This research was supported in part by a grant from Mitsubishi Pharma Research Foundation, and a grant from Japan Leukemia Research Fund.

PY - 2006/7/15

Y1 - 2006/7/15

N2 - Core sequences necessary for substrate recognition and its inhibition at the PR/p3 site of HTLV-1 protease were clarified for the first time. From the cleavage rates of peptides containing a part of the PR/p3 site, a heptapeptide was found to be the minimal sequence required for substrate recognition. The use of synthetic inhibitors containing hydroxyethylamine dipeptide isostere indicated that a tetrapeptide sequence was necessary to achieve potent inhibition.

AB - Core sequences necessary for substrate recognition and its inhibition at the PR/p3 site of HTLV-1 protease were clarified for the first time. From the cleavage rates of peptides containing a part of the PR/p3 site, a heptapeptide was found to be the minimal sequence required for substrate recognition. The use of synthetic inhibitors containing hydroxyethylamine dipeptide isostere indicated that a tetrapeptide sequence was necessary to achieve potent inhibition.

KW - HTLV-1 protease

KW - Hydroxyethylamine dipeptide isostere

KW - Inhibitor

KW - Substrate specificity

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Evaluations of substrate specificity and inhibition at PR/p3 cleavage site of HTLV-1 protease

Abstract

Keywords

ASJC Scopus subject areas

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