Faculty of Pharmaceutical Sciences, Hokuriku University.
SCRUM Inc.
Biol Pharm Bull. 2021;44(4):515-521. doi: 10.1248/bpb.b20-00799.
In 2017, Leoni et al. reported myticalins as novel cationic linear antimicrobial peptides obtained from marine mussels. The authors focused on myticalin A6 (29 amino acids), which has a relatively short chain length among myticalins and contains a repeating X-proline(Pro)-arginine (Arg) sequence in its structure. We investigated the antimicrobial activity of myticalin A6 against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (S. aureus). Fragment derivatives of myticalin A6 were synthesized, and the site required for expression of antimicrobial activity was examined. To investigate the structure-antimicrobial activity relationship of myticalin A6, short-chain derivatives and partially substituted derivatives were synthesized, and the antimicrobial activity was measured. Furthermore, some cyclized derivatives were synthesized and examined for antimicrobial activity. Circular dichroism (CD) spectroscopy of myticalin A6 and its derivatives was carried out to evaluate the secondary structure. Myticalin A6 exhibited an antimicrobial activity of 1.9 µM against S. aureus. Myticalin A6 (3-23)-OH (21 amino acids) exhibited an antimicrobial activity of 2.4 µM against S. aureus, suggesting that the X-Pro-Arg repeat sequence is important for antimicrobial activity. Derivatives with different CD measurement results from myticalin A6 (3-23)-OH exhibited decreased activity. The myticalin A6 (3-23)-OH derivative in which all Arg residues were replaced with lysine (Lys) residues exhibited reduced antimicrobial activity against S. aureus. We succeeded in synthesizing cyclic derivatives using 9-fluorenylmethoxycarbonyl (Fmoc)-aspartic acid (Asp)(Wang resin)-[2-phenylisopropyl ester (OPis)], but the yield of derivatives with 21 amino acids was decreased. The myticalin derivatives synthesized in this study did not exhibit any enhancement in antimicrobial activity due to cyclization.
2017 年，Leoni 等人报道了作为新型阳离子线性抗菌肽的 myticalin，它们来源于海洋贻贝。作者关注 myticalin A6（29 个氨基酸），它在 myticalin 中具有相对较短的链长，并且在其结构中含有重复的 X-脯氨酸（Pro）-精氨酸（Arg）序列。我们研究了 myticalin A6 对大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌（S. aureus）的抗菌活性。合成了 myticalin A6 的片段衍生物，并检查了表达抗菌活性所需的位点。为了研究 myticalin A6 的结构-抗菌活性关系，合成了短链衍生物和部分取代衍生物，并测量了抗菌活性。此外，还合成了一些环化衍生物并检查了其抗菌活性。通过圆二色性（CD）光谱法对 myticalin A6 及其衍生物进行了结构评估。Myticalin A6 对 S. aureus 的抗菌活性为 1.9 μM。Myticalin A6（3-23）-OH（21 个氨基酸）对 S. aureus 的抗菌活性为 2.4 μM，表明 X-Pro-Arg 重复序列对抗菌活性很重要。与 myticalin A6（3-23）-OH 的 CD 测量结果不同的衍生物表现出降低的活性。所有 Arg 残基均被赖氨酸（Lys）残基取代的 myticalin A6（3-23）-OH 衍生物对 S. aureus 的抗菌活性降低。我们成功地使用 9-芴甲氧羰基（Fmoc）-天冬氨酸（Asp）（Wang 树脂）-[2-苯异戊酯（OPis）]合成了环状衍生物，但具有 21 个氨基酸的衍生物的产率降低。本研究合成的 myticalin 衍生物由于环化没有表现出任何增强的抗菌活性。
