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.
Kohei Tsuji  1 ,  Rongyi Wang  1 ,  Takuya Kobayakawa  1 ,  Kofi Baffour-Awuah Owusu  2 ,  Masayuki Fujino  3 ,  Moemi Kaneko  1 ,  Naoki Yamamoto  4 ,  Tsutomu Murakami  5 ,  Hirokazu Tamamura  6
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: [email protected].
  • 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: [email protected].
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.