title: A novel ranacyclin-like peptide with anti-platelet activity identified from skin secretions of the frog Amolops loloensis.
abstract: Albeit many bioactive peptides have been reported from amphibian skins, no anti-platelet peptide has been identified till to date. Here, an anti-platelet peptide, namely Zongdian platelet inhibitor (ZDPI), with the molecular weight of 1798.6 Da, was purified and characterized from skin secretions of the frog, Amolops loloensis. The amino acid sequence of ZDPI was determined as FRGCWLKNYSPRGCL-NH2 by combination methods of Edman degradation, mass spectrometry analysis and carboxypeptidase Y treatment revealing that it is composed of 15 amino acid residues with two cysteines formed an intra-molecular disulfide bridge and C-terminal amidation. cDNA encoding ZDPI precursor was cloned from skin cDNA library of A. loloensis. The precursor is composed of 63 amino acid (aa) residues including the predicted signal peptide (22 aa), an acidic spacer peptide (19 aa), and mature ZDPI. BLAST search indicates that ZDPI belongs to antimicrobial peptide family of ranacyclin, peptide leucine arginine or odorranain. It was found to inhibit ADP-induced platelet aggregation in a dose-dependent manner. At the concentration of 32 μg/ml, ZDPI completely inhibited platelet aggregation induced by ADP. To the best of our knowledge, this is the first report about an anti-platelet peptide from amphibian skin secretions. Considering its strong inhibitory ability on platelets and simple structure, ZDPI might be an excellent candidate or template to develop anti-thrombosis agent. In addition, the discovery of anti-platelet peptide in the frog skin increases biological function spectrum of amphibian skin peptides.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; Graduate University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; Graduate University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; Graduate University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.affiliation: Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; Joint Laboratory of Natural Peptide of University of Science and Technology of China & Kunming Institute of Zoology, Chinese Academy of Sciences, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; Joint Laboratory of Natural Peptide of University of Science and Technology of China & Kunming Institute of Zoology, Chinese Academy of Sciences, China. Electronic address: lvqm@mail.kiz.ac.cn.
authors.forename: Qiumin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001001:Anura / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010456:Peptides, Cyclic / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011898:Ranidae; D012867:Skin / Q000378:metabolism*
chemical_list: D029845:Amphibian Proteins; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; D011498:Protein Precursors
keywords: Amolops loloensis; Amphibian; Anti-platelet; Skin secretion