2. Academic Validation
  3. Exploratory studies on CA-15L, an anti-HIV active HIV-1 capsid fragment

Exploratory studies on CA-15L, an anti-HIV active HIV-1 capsid fragment

  • Bioorg Med Chem. 2020 Jun 1;28(11):115488. doi: 10.1016/j.bmc.2020.115488.
Kohei Tsuji 1,  Kofi Baffour-Awuah Owusu 2,  Takuya Kobayakawa 1,  Rongyi Wang 1,  Masayuki Fujino 3,  Moemi Kaneko 1,  Naoki Yamamoto 4,  Tsutomu Murakami 5,  Hirokazu Tamamura 6
Affiliations

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 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: 32305183 DOI: 10.1016/j.bmc.2020.115488
Abstract

Utilizing overlapping fragment peptide libraries covering the whole sequence of an HIV-1 capsid (CA) protein with the addition of an octa-arginyl moiety, we had previously found several Peptides with anti-HIV-1 activity. Herein, among these potent CA fragment Peptides, CA-15L was examined because this peptide sequence overlaps with Helix 7, a helix region of the CA protein, which may be important for oligomerization of the CA proteins. A CA-15L surrogate with hydrophilic residues, and its derivatives, in which amino acid sequences are shifted toward the C-terminus by one or more residues, were synthesized and their anti-HIV activity was evaluated. In addition, its derivatives with substitution for the Ser149 residue were synthesized and their anti-HIV activity was evaluated because Ser149 might be phosphorylated in the step of degradation of CA protein oligomers. Several active compounds were found and might become new anti-HIV agents and new tools for elucidation of CA functions.

Keywords

Anti-HIV-1 activity; Capsid protein; Hydrophilic residue; Octa-arginyl group.

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