Pachymedusa dacnicolor tryptophyllin-1: structural characterization, pharmacological activity and cloning of precursor cDNA

TB Chen, DF Orr, M O'Rourke, C McLynn, AJ Bjourson, Stephen McClean, D Hirst, PF Rao, C Shaw

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Tryptophyllins are a heterogenous group of amphibian skin peptides originally identified in skin extracts of Neotropical leaf frogs, Phyllomedusa sp., by chemical means. Until now, biosynthetic precursor structure and biological activity remain unreported. Here we describe the isolation of a novel, post-translationally modified tryptophyllin, Lys-Pro-Hyp-Ala-Trp-Val-Pro.amide (PdT-1), from the skin secretion of the Mexican leaf frog, Pachymedusa dacnicolor. Using a 3'- and 5'-RACE strategy and an in vitro skin cDNA library, the PdT-1 encoding precursor was cloned and found to consist of an open-reading frame of 62 amino acids with a single copy of PdT-1 located towards the C-terminus. A synthetic replicate of PdT-1 was found to be a potent myoactive agent, relaxing mammalian arterial smooth muscle and contracting small intestinal smooth muscle at nanomolar concentrations. PdT-1 is thus the first amphibian skin tryptophyllin to be pharmacologically characterized and the first whose precursor cDNA has been cloned. (C) 2003 Elsevier B.V. All rights reserved.
LanguageEnglish
Pages25-32
JournalRegulatory Peptides
Volume117
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Organism Cloning
Complementary DNA
Pharmacology
Skin
Amphibians
Anura
Smooth Muscle
Gene Library
Amides
Open Reading Frames
tryptophyllins
Amino Acids
Peptides

Cite this

Chen, TB ; Orr, DF ; O'Rourke, M ; McLynn, C ; Bjourson, AJ ; McClean, Stephen ; Hirst, D ; Rao, PF ; Shaw, C. / Pachymedusa dacnicolor tryptophyllin-1: structural characterization, pharmacological activity and cloning of precursor cDNA. In: Regulatory Peptides. 2004 ; Vol. 117, No. 1. pp. 25-32.
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Pachymedusa dacnicolor tryptophyllin-1: structural characterization, pharmacological activity and cloning of precursor cDNA. / Chen, TB; Orr, DF; O'Rourke, M; McLynn, C; Bjourson, AJ; McClean, Stephen; Hirst, D; Rao, PF; Shaw, C.

In: Regulatory Peptides, Vol. 117, No. 1, 01.2004, p. 25-32.

Research output: Contribution to journalArticle

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