title: Molecular cloning of a novel tryptophyllin peptide from the skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis.
abstract: Tryptophyllins are a group of small (4-14 amino acids), heterogenous peptides, mostly from the skins of hylid frogs from the genera, Phyllomedusa and Litoria. To date, more than forty TPHs have been discovered in species from these two genera. Here, we describe the identification of a novel tryptophyllin type 3 peptide, PhT-3, from the extracts of skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis, and molecular cloning of its precursor-encoding cDNA from a cDNA library constructed from the same skin sample. Full primary structural characterization was achieved using a combination of direct Edman degradation, mass spectrometry and deduction from cloned skin-derived cDNA. The open-reading frame of the precursor cDNA was found to consist of 63 amino acid residues. The mature peptide arising from this precursor contains a post-translationally modified N-terminal pyroglutamate (pGlu) residue, formed from acid-mediated cyclization of an N-terminal Gln (Q) residue, and with the structure: pGlu-Asp-Lys-Pro-Phe-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met. Pharmacological assessment of a synthetic replicate of this peptide on phenylephrine preconstricted rat tail artery segments, revealed a reduction in relaxation induced by bradykinin. PhT-3 was also found to mediate antiproliferative effects on human prostate cancer cell lines.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; School of Pharmacy, Medical Biology Centre, Queen's University, Belfast, BT9 7BL, UK.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Lin
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D019151:Peptide Library; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D012867:Skin
chemical_list: D009842:Oligopeptides; D019151:Peptide Library; C000595094:tryptophyllin type 3 peptide, PhT-3; C048291:tryptophyllins
keywords: Phyllomedusa hypochondrialis; Tryptophyllins; amphibian skin peptide; anticancer effect; bradykinin antagonist