Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, UK.
Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, UK.
Biochimie. 2024 Aug;223:23-30. doi: 10.1016/j.biochi.2024.03.012. Epub 2024 Mar 30.
Five host-defense peptides (figainin 2PL, hylin PL, raniseptin PL, plasticin PL, and peptide YL) were isolated from norepinephrine-stimulated skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae) collected in Trinidad. Raniseptin PL (GVFDTVKKIGKAVGKFALGVAKNYLNS.NH) and figainin 2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ. NH) showed potent and rapid bactericidal activity against a range of clinically relevant Gram-positive and Gram-negative ESKAPE pathogens and Clostridioides difficile. The peptides also showed potent cytotoxic activity (LC values < 30 μM) against A549, MDA-MB-231 and HT29 human tumor-derived cell lines but appreciably lower hemolytic activity against mouse erythrocytes (LC = 262 ± 14 μM for raniseptin PL and 157 ± 16 μM for figainin 2PL). Hylin PL (FLGLIPALAGAIGNLIK.NH) showed relatively weak activity against microorganisms but was more hemolytic. The glycine-leucine-rich peptide with structural similarity to the plasticins (GLLSTVGGLVGGLLNNLGL.NH) and the non-cytotoxic peptide YL (YVPGVIESLL.NH) lacked antimicrobial and cytotoxic activities. Hylin PL, raniseptinPL and peptide YL stimulated the rate of release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥100 nM. Peptide YL was the most effective (2.3-fold increase compared with basal rate at 1 μM concentration) and may represent a template for the design of a new class of incretin-based anti-diabetic drugs.
从在特立尼达收集的香蕉树栖蛙(Boana platanera)的去甲肾上腺素刺激的皮肤分泌物中分离出五种宿主防御肽(figainin 2PL、hylin PL、raniseptin PL、plasticin PL 和 peptide YL)。Raniseptin PL(GVFDTVKKIGKAVGKFALGVAKNYLNS.NH)和 figainin 2PL(FLGTVLKLGKAIAKTVVPMLTNAMQPKQ. NH)对一系列临床相关的革兰氏阳性和革兰氏阴性 ESKAPE 病原体和艰难梭菌具有强大而快速的杀菌活性。这些肽还对 A549、MDA-MB-231 和 HT29 人肿瘤衍生细胞系表现出强大的细胞毒性活性(LC 值<30 μM),但对小鼠红细胞的溶血活性明显较低(LC 为 262±14 μM 对于 raniseptin PL 和 157±16 μM 对于 figainin 2PL)。Hylin PL(FLGLIPALAGAIGNLIK.NH)对微生物的活性相对较弱,但溶血作用更强。与 plastins 结构相似的富含甘氨酸和亮氨酸的肽(GLLSTVGGLVGGLLNNLGL.NH)和非细胞毒性肽 YL(YVPGVIESLL.NH)缺乏抗菌和细胞毒性活性。Hylin PL、raniseptinPL 和 peptide YL 在浓度≥100 nM 时刺激 BRIN-BD11 克隆β细胞胰岛素释放率。Peptide YL 是最有效的(在 1 μM 浓度时与基础速率相比增加了 2.3 倍),可能代表了设计新型肠促胰岛素类抗糖尿病药物的模板。