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  3. Anti-HIV screening for cell-penetrating peptides using chloroquine and identification of anti-HIV peptides derived from matrix proteins

Anti-HIV screening for cell-penetrating peptides using chloroquine and identification of anti-HIV peptides derived from matrix proteins

  • Bioorg Med Chem. 2015 Aug 1;23(15):4423-4427. doi: 10.1016/j.bmc.2015.06.020.
Takaaki Mizuguchi 1,  Nami Ohashi 1,  Wataru Nomura 1,  Mao Komoriya 1,  Chie Hashimoto 1,  Naoki Yamamoto 2,  Tsutomu Murakami 3,  Hirokazu Tamamura 4
Affiliations

Affiliations

  • 1 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
  • 2 Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
  • 3 AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. Electronic address: tmura@nih.go.jp.
  • 4 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address: tamamura.mr@tmd.ac.jp.
PMID: 26094944 DOI: 10.1016/j.bmc.2015.06.020
Abstract

Previously, compounds which inhibit the HIV-1 replication cycle were found in overlapping peptide libraries covering the whole sequence of an HIV-1 matrix (MA) protein constructed with the addition of an octa-arginyl group. The two top lead compounds are sequential fragments MA-8L and MA-9L. In the present study, the addition of chloroquine in cell-based anti-HIV assays was proven to be an efficient method with which to find anti-HIV compounds among several Peptides conjugated by cell-penetrating signals such as an octa-arginyl group: the conjugation of an octa-arginyl group to individual Peptides contained in whole proteins in combination with the addition of chloroquine in cells is a useful assay method to search active Peptides. To find more potent fragment Peptides, individual Peptides between MA-8L and MA-9L, having the same peptide chain length but with sequences shifted by one amino acid residue, were synthesized in this paper and their anti-HIV activity was evaluated with an anti-HIV assay using chloroquine. As a result, the Peptides in the C-terminal side of the series, which are relatively close to MA-9L, showed more potent inhibitory activity against both X4-HIV-1 and R5-HIV-1 than the Peptides in the N-terminal side.

Keywords

Anti-HIV; Chloroquine; Matrix protein; Octa-arginyl group.

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