A Review on Bradykinin-Related Peptides Isolated from Amphibian Skin Secretion

Abstract

Amphibian skin secretion has great potential for drug discovery and contributes hundreds of bioactive peptides including bradykinin-related peptides (BRPs). More than 50 BRPs have been reported in the last two decades arising from the skin secretion of amphibian species. They belong to the families Ascaphidae (1 species), Bombinatoridae (3 species), Hylidae (9 speices) and Ranidae (25 species). This paper presents the diversity of structural characteristics of BRPs with N-terminal, C-terminal extension and amino acid substitution. The further comparison of cDNA-encoded prepropeptides between the different species and families demonstrated that there are various forms of kininogen precursors to release BRPs and they constitute important evidence in amphibian evolution. The pharmacological activities of isolated BRPs exhibited unclear structure–function relationships, and therefore the scope for drug discovery and development is limited. However, their diversity shows new insights into biotechnological applications and, as a result, comprehensive and systematic studies of the physiological and pharmacological activities of BRPs from amphibian skin secretion are needed in the future.

Species-specific pharmacology of maximakinin, an amphibian homologue of bradykinin: putative prodrug activity at the human B2receptor and peptidase resistance in rats

“…Strong species-specific responses to a toxin-derived peptide such as MK is plausible (Xi et al, 2015) and its empirically discovered prodrug status in human systems suggests important differences of the topography of the interface between the B 2 R and extracellular fluid across mammalian species. Unlike other BK homologues found in venoms, such as Polistes kinin, MK is not an efficient mast cell activator but its metabolic resilience may contribute to its toxicity in relevant predator species of B. maxima .…”

“…Several such BK-related peptides of amphibian origin are believed to have co-evolved with the kinin receptors of the predatory species such as birds and snakes (Xi et al, 2015). Further, Polistes kinin, from a wasp venom, is a comparable peptide possessing the BK sequence at its C-terminus and possessing a hydrophilic N-terminal extension; it has been reported a long time ago that Polistes kinin releases histamine from mast cells, but that BK doesn’t (Johnson & Erdös, 1973).…”

Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions

“…Both the Amolopkinin-W1 and Amolopkinin-W2 exhibited inhibitory effect of BK-induced intestinal smooth muscle contraction, while no direct effects on bladder and uterine smooth muscle preparations were detected [14]. Despite the fact that the precise functions of diverse N - or C -terminal extension of BRPs still remains elusive, they are predicted to be involved in prolonging the interaction time of these peptides as ligands with target receptors, which could be adopted as a defensive strategy by host to survival [18,19]. …”

Chemical Methods for N‐ and O‐Sulfation of Small Molecules, Amino Acids and Peptides

“…To test the hypothesis for site‐selective sulfamation, a trimer (glutathione, 31 ) and a nonamer (bradykinin, 33 ) peptide sequence were selected (Scheme ) . In particular, bradykinin is a representative member of the vasoactive kinin class of cardioprotective peptides, and known to be secreted as sulfates in mammals . Treatment of glutathione gave rise to a single product, 32 , monosulfated at the N‐terminal amine of glutamic acid.…”