Abstract |
In this study, the effects of side-chain configurations of D-Ile residues of a retro-inverso (RI)-type inhibitor on the human T-cell leukemia virus type 1 (HTLV-1) protease containing a hydroxyethylamine dipeptide isostere were clarified. Prior to evaluation using the RI-type inhibitor, the effects of side-chain configurations of Ile residues of the substrate peptide on the HTLV-1 protease were examined to estimate the influence of side-chain configurations on enzyme activity. Based on the estimation of the influence of side-chain configurations on protease affinity, the RI-type inhibitors containing a D-allo-Ile residue in the corresponding substrate sequence, instead of a D-Ile residue, were synthesized via 9-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis. Refolded recombinant HTLV-1 protease (1-116, L40I) was used for the simple and short evaluation of the inhibitory activities of the synthesized RI-type inhibitors. The results clearly indicated that mimicking the whole topology, comprising both the main- and side-chain structures of the parent inhibitor, is effective for the design of potent RI-modified protease inhibitors.
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Authors | Chiyuki Awahara, Daiki Oku, Saki Furuta, Kazuya Kobayashi, Kenta Teruya, Kenichi Akaji, Yasunao Hattori |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 27
Issue 5
(Mar 02 2022)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 35268749
(Publication Type: Journal Article)
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Chemical References |
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