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从栖息在香蕉树上的青蛙 Boana platanera(树蛙科;雨蛙亚科)的皮肤分泌物中分离出的多功能宿主防御肽。

Multifunctional host-defense peptides isolated from skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae).

机构信息

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.

出版信息

Biochimie. 2024 Aug;223:23-30. doi: 10.1016/j.biochi.2024.03.012. Epub 2024 Mar 30.

Abstract

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.

摘要

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。

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