Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
College of Basic Medical Science, Zhejiang Chinese Medial University, Hangzhou 310053, China.
Molecules. 2017 Oct 24;22(10):1805. doi: 10.3390/molecules22101805.
The dermaseptin peptides, mainly derived from the skin secretions of Hylidae frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse antimicrobial and anticancer activities with low cytotoxicity. Here, we reported a novel dermaseptin peptide, from the South American orange-legged leaf frogs, (Phyllomedusa) , processing the shortest peptide length, namely Dermaseptin-PH. The complementary DNA (cDNA) encoding biosynthetic precursor of Dermaseptin-PH was initially identified by the rapid amplification of cDNA ends PCR (RACE-PCR) technique from the skin secretion. The predicted primary structure was confirmed by a combination of reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS fragmentation from the skin secretion. Chemically-synthetic Dermaseptin-PH was investigated using a range of bioactivity assessment assays to evaluate the biological activities and cytotoxicity of Dermaseptin-PH. Dermaseptin-PH inhibited the growth of Gram-negative bacteria, Gram-positive bacteria, and pathogenic yeast . In addition, Dermaseptin-PH showed a broad-spectrum of anticancer activities against several cancer cell lines including MCF-7, H157, U251MG, MDA-MB-435S, and PC-3. The potent antimicrobial and anticancer activities of Dermaseptin-PH make it a promising candidate in the discovery of new drugs for clinical applications, and the relatively short sequence of Dermaseptin-PH can provide new insight for the research and structural modification of new peptide drugs.
从雨蛙科青蛙皮肤分泌物中主要获得的天蚕素肽属于一类抗菌肽超家族,具有多种抗菌和抗癌活性,同时细胞毒性低。在此,我们报道了一种来自南美洲橙腿叶蛙(Phyllomedusa)的新型天蚕素肽,即 Dermaseptin-PH,其具有最短的肽长度。通过快速扩增 cDNA 末端 PCR(RACE-PCR)技术从皮肤分泌物中最初鉴定出编码 Dermaseptin-PH 生物合成前体的 cDNA。通过从皮肤分泌物中进行反相高效液相色谱(RP-HPLC)和 MS/MS 片段组合来确认预测的一级结构。使用一系列生物活性评估测定法对化学合成的 Dermaseptin-PH 进行研究,以评估 Dermaseptin-PH 的生物学活性和细胞毒性。Dermaseptin-PH 抑制革兰氏阴性菌、革兰氏阳性菌和致病性酵母的生长。此外,Dermaseptin-PH 对几种癌细胞系(包括 MCF-7、H157、U251MG、MDA-MB-435S 和 PC-3)具有广谱的抗癌活性。Dermaseptin-PH 的强大抗菌和抗癌活性使其成为临床应用新药发现的有前途的候选物,而 Dermaseptin-PH 相对较短的序列可以为新型肽药物的研究和结构修饰提供新的见解。