Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
Vital Resources Applied Laboratory, Inc., Iizuka 820-0067, Japan.
Molecules. 2023 Apr 10;28(8):3337. doi: 10.3390/molecules28083337.
One of the most striking aspects of the primary structure in the hydrophobic domains of the tropoelastin molecule is the occurrence of the VAPGVG repeating sequence. Since the N-terminal tripeptide VAP of VAPGVG showed a potent ACE inhibitory activity, the ACE inhibitory activity of various derivatives of VAP was examined in vitro. The results showed that VAP derivative peptides VLP, VGP, VSP, GAP, LSP, and TRP exhibited potent ACE inhibitory activities, while the non-derivative peptide APG showed only weak activity. In in silico studies, the docking score S value showed that VAP derivative peptides VLP, VGP, VSP, LSP, and TRP had stronger docking interactions than APG. Molecular docking in the ACE active pocket showed that TRP, the most potent ACE inhibitory peptide among the VAP derivatives, had a larger number of interactions with ACE residues in comparison with APG and that the TRP molecule appeared to spread widely in the ACE pocket, while the APG molecule appeared to spread closely. Differences in molecular spread may be a reason why TRP exhibits more potent ACE inhibitory activity than APG. The results suggest that the number and strength of interactions between the peptide and ACE are important for the ACE- inhibitory potency of the peptide.
弹性蛋白原分子疏水区一级结构最显著的特点之一是 VAPGVG 重复序列的出现。由于 VAPGVG 中 N 端三肽 VAP 具有很强的 ACE 抑制活性，因此在体外研究了 VAP 的各种衍生物的 ACE 抑制活性。结果表明，VAP 衍生肽 VLP、VGP、VSP、GAP、LSP 和 TRP 具有很强的 ACE 抑制活性，而非衍生肽 APG 仅表现出较弱的活性。在计算机模拟研究中，对接评分 S 值表明，VAP 衍生肽 VLP、VGP、VSP、LSP 和 TRP 与 APG 相比具有更强的对接相互作用。在 ACE 活性口袋中的分子对接表明，VAP 衍生物中最有效的 ACE 抑制肽 TRP 与 ACE 残基的相互作用数量多于 APG，并且 TRP 分子似乎在 ACE 口袋中广泛展开，而 APG 分子似乎紧密展开。分子扩散的差异可能是 TRP 比 APG 表现出更强的 ACE 抑制活性的原因之一。研究结果表明，肽与 ACE 之间的相互作用数量和强度对肽的 ACE 抑制活性很重要。
