Abstract
The defensive skin secretions of amphibians are a rich resource for the discovery of novel, bioactive peptides. Here we report the identification of a novel vascular smooth muscle-relaxing peptide, named vasorelaxin, from the skin secretion of the Chinese piebald odorous frog, Odorrana schmackeri. Vasorelaxin consists of 20 amino acid residues, SRVVKCSGFRPGSPDSREFC, with a disulfide-bridge between Cys-6 and Cys-20. The structure of its biosynthetic precursor was deduced from cloned skin cDNA and consists of 67 amino acid residues encoding a single copy of vasorelaxin (vasorelaxin, accession number: HE860494). Synthetic vasorelaxin caused a profound relaxation of rat arterial smooth muscle with an EC50 of 6.76 nM.
Highlights
The failure of the chemical approach to expand and replenish the drug pipelines of the pharmaceutical industry has led to a renaissance in natural drug discovery, especially in so-called ‘‘biologics’’ [1,2]
Amphibian skin secretions continue to be validated as unique sources of novel biologically-active peptides [3,9,10]
The pharmacologically-active peptides of amphibian skin can generally be regarded as sitesubstituted analogs of endogenous vertebrate regulatory peptides and can be classified into known families of such, examples being the bradykinins, tachykinins and bombesins [22,23,24]
Summary
The failure of the chemical approach to expand and replenish the drug pipelines of the pharmaceutical industry has led to a renaissance in natural drug discovery, especially in so-called ‘‘biologics’’ [1,2]. Focused studies on the bioactive components of these secretions have shown unequivocally, that they are unique sources of a plethora of potent biologically-active molecules that act on an array of endogenous mammalian/human molecular targets, many of which are diseaseassociated [3,4,5,6,7,8] These amphibian skin-derived molecules are thought to represent the fundamental components of an intrinsic survival mechanism that has obviously served amphibians well for many millions of years. With increasingly focused efforts directed towards amphibian skin peptidome characterization, prototypes of novel families have been recently-discovered that include kassorins [11], limnonectins, [12], sauvatides [13] and kasstasin [14] The latter peptide is a vasoconstrictor peptide as determined by its high potency in contracting rat tail artery smooth muscle
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