Xi Xinping, Li Bin, Chen Tianbao, Kwok Hang Fai
Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR, China.
Natural Drug Discovery Group, School of Pharmacy, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK.
Toxins (Basel). 2015 Mar 18;7(3):951-70. doi: 10.3390/toxins7030951.
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.
两栖动物皮肤分泌物在药物发现方面具有巨大潜力,可产生数百种生物活性肽,包括缓激肽相关肽(BRP)。在过去二十年中,已报道了50多种源自两栖动物皮肤分泌物的BRP。它们属于尾蟾科(1种)、铃蟾科(3种)、雨蛙科(9种)和蛙科(25种)。本文介绍了具有N端、C端延伸和氨基酸取代的BRP的结构特征多样性。不同物种和科之间cDNA编码的前原肽的进一步比较表明,存在多种形式的激肽原前体来释放BRP,它们构成了两栖动物进化的重要证据。分离出的BRP的药理活性显示出不明确的构效关系,因此药物发现和开发的范围有限。然而,它们的多样性为生物技术应用提供了新的见解,因此,未来需要对两栖动物皮肤分泌物中的BRP的生理和药理活性进行全面系统的研究。