Potent leads based on CA-19L, an anti-HIV active HIV-1 capsid fragment

Kohei Tsuji; Rongyi Wang; Takuya Kobayakawa; Kofi Baffour-Awuah Owusu; Masayuki Fujino; Moemi Kaneko; Naoki Yamamoto; Tsutomu Murakami; Hirokazu Tamamura

doi:10.1016/j.bmc.2020.115923

Potent leads based on CA-19L, an anti-HIV active HIV-1 capsid fragment

Bioorg Med Chem. 2021 Jan 15:30:115923. doi: 10.1016/j.bmc.2020.115923. Epub 2020 Dec 7.

Authors

Kohei Tsuji¹, Rongyi Wang¹, Takuya Kobayakawa¹, Kofi Baffour-Awuah Owusu², Masayuki Fujino³, Moemi Kaneko¹, Naoki Yamamoto⁴, Tsutomu Murakami⁵, Hirokazu Tamamura⁶

Affiliations

¹ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
² Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8150, Japan.
³ AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
⁴ Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8150, Japan; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
⁵ AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Electronic address: tmura@nih.go.jp.
⁶ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8150, Japan. Electronic address: tamamura.mr@tmd.ac.jp.

PMID: 33316719
DOI: 10.1016/j.bmc.2020.115923

Abstract

Several anti-HIV-1 peptides have previously been found among overlapping fragment peptide libraries that contain an octa-arginyl moiety and cover the whole sequence of an HIV-1 capsid (CA) protein. Several derivatives based on a potent CA fragment peptide CA-19L have been synthesized. CA-19L overlaps with the Helix 9 region of the CA protein, which could be important for oligomerization of the CA proteins. Derivatives of CA-19L in which several amino acid residues were added to the N- and C-termini according to the natural CA sequence, were synthesized and their anti-HIV activity was evaluated. Some potent compounds were found, and these potential new anti-HIV agents are expected to be useful as new tools for elucidation of CA functions.

Keywords: Anti-HIV-1 activity; Capsid protein; Octa-arginyl group; Oligomerization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
Capsid Proteins / antagonists & inhibitors*
Capsid Proteins / metabolism
Dose-Response Relationship, Drug
HIV-1 / drug effects*
Humans
Microbial Sensitivity Tests
Protein Conformation
Structure-Activity Relationship

Substances

Anti-HIV Agents
Capsid Proteins