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

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-03-30 DOI:10.1016/j.biochi.2024.03.012

J. Michael Conlon , Ananyaa Sridhar , Dawood Khan , Taylor S. Cunning , Jack J. Delaney , Megan G. Taggart , Nigel G. Ternan , Jérôme Leprince , Laurent Coquet , Thierry Jouenne , Samir Attoub , Milena Mechkarska

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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.NH₂) and figainin 2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ. NH₂) 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 (LC₅₀ values < 30 μM) against A549, MDA-MB-231 and HT29 human tumor-derived cell lines but appreciably lower hemolytic activity against mouse erythrocytes (LC₅₀ = 262 ± 14 μM for raniseptin PL and 157 ± 16 μM for figainin 2PL). Hylin PL (FLGLIPALAGAIGNLIK.NH₂) showed relatively weak activity against microorganisms but was more hemolytic. The glycine-leucine-rich peptide with structural similarity to the plasticins (GLLSTVGGLVGGLLNNLGL.NH₂) and the non-cytotoxic peptide YL (YVPGVIESLL.NH₂) 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.

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从香蕉树栖蛙 Boana platanera (Hylidae; Hylinae) 皮肤分泌物中分离出的多功能宿主防御肽。

从特立尼达岛采集的香蕉树栖蛙 Boana platanera（蹄蟾科；蹄蟾属）的去甲肾上腺素刺激皮肤分泌物中分离出了五种宿主防御肽（无花果素 2PL、蹄蟾素 PL、雷尼塞素 PL、塑性素 PL 和肽 YL）。Raniseptin PL（GVFDTVKKIGKAVGKFALGVAKNYLNS.NH2）和 figainin 2PL （FLGTVLKLGKAIAKTVVPMLTNAMQP KQ.NH2）对一系列临床相关的革兰氏阳性和革兰氏阴性 ESKAPE + 病原体以及艰难梭菌具有强效和快速的杀菌活性。这些肽还显示出强大的细胞毒活性（LC50 值 50 = 262 ± 14 μM（raniseptin PL）和 157 ± 16 μM（figainin 2PL））。Hylin PL（FLGLIPALAGAIGNLIK.NH2）对微生物的活性相对较弱，但溶血作用更强。与塑化素结构相似的富含甘氨酸-亮氨酸的多肽（GLLSTVGGLVGGLL NNLGL.NH2）和无细胞毒性的多肽 YL（YVPGVIESLL.NH2）缺乏抗菌和细胞毒性活性。在浓度≥100 nM时，Hylin PL、raniseptin-PL和肽YL可刺激BRIN-BD11克隆β细胞释放胰岛素。多肽 YL 的效果最好（与 1 μM 浓度下的基础速率相比，增加了 2.3 倍），可能是设计一类基于增量素的新型抗糖尿病药物的模板。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567