Amiche Mohamed
Biol Aujourdhui. 2016;210(2):101-17. doi: 10.1051/jbio/2016015. Epub 2016 Sep 30.
The search for new bioactive molecules that could be used in therapeutics is a major public health issue, particularly in the treatment of certain diseases such as cancer. In this context the exploration of the venom of animals (snakes, amphibians, cones, scorpions, insects...) that produce molecules of various structures and biological activities, is a very promising direction. Research in this area led to the discovery of neuropeptides, hormones, toxins, antimicrobial peptides and other extremely potent mediators. These are now used in many areas both in fundamental research and in translational research, respectively, to understand biochemical and physiological mechanisms, or to use as medical diagnostic tools and for therapeutic purposes. Pr. V. Erspamer is the first researcher to have shown, in the 1930s, that in addition to biogenic amines and alkaloids, granular glands from the skin of amphibians also produced huge amounts of peptides with various structures and biological activities. He also showed that these peptides had their counterparts, most often in the form of identical or similar peptides, in the central nervous system and the gastrointestinal tract of mammals. These observations are summarized in the form of a triangle concept of "brain-gut-skin" that states that any peptide found in a compartment should be present in the other two. In addition, abundance, ease of extraction and identification of peptides from amphibian skin make this model a means to search for their counterparts in mammals where they are present in minute quantities. This approach has two advantages: (i) at the fundamental level, the large peptide diversity, ubiquity and multiplicity of functions to which they participate, constitute a true chemical library to understand the mechanisms of recognition and signal transduction and study the physicochemical basic of the specificity; and (ii) in terms of applications, the relative simplicity of these peptides and the rise of the production techniques by chemical or recombinant synthesis offer an innovative potential for the development of molecules with pharmacological or therapeutic purposes.
寻找可用于治疗的新型生物活性分子是一个重大的公共卫生问题，尤其是在治疗某些疾病（如癌症）方面。在这种背景下，探索产生具有各种结构和生物活性分子的动物毒液（蛇、两栖动物、芋螺、蝎子、昆虫等）是一个非常有前景的方向。该领域的研究导致了神经肽、激素、毒素、抗菌肽和其他极其有效的介质的发现。如今，这些物质分别在基础研究和转化研究的许多领域中得到应用，用于理解生化和生理机制，或用作医学诊断工具及治疗目的。V. 埃斯帕默教授是首位在20世纪30年代表明，除了生物胺和生物碱外，两栖动物皮肤的颗粒腺还能产生大量具有各种结构和生物活性的肽的研究人员。他还表明，这些肽在哺乳动物的中枢神经系统和胃肠道中也有对应物，且大多以相同或相似肽的形式存在。这些观察结果以“脑-肠-皮肤”三角概念的形式进行了总结，即任何在一个隔室中发现的肽都应存在于其他两个隔室中。此外，从两栖动物皮肤中提取和鉴定肽的丰富性、简便性，使得该模型成为在哺乳动物中寻找微量存在的对应物的一种手段。这种方法有两个优点：（i）在基础层面，肽的多样性大、普遍存在且参与多种功能，构成了一个真正的化学库，有助于理解识别和信号转导机制，并研究特异性的物理化学基础；（ii）在应用方面，这些肽相对简单，且化学或重组合成生产技术的兴起为开发具有药理或治疗目的的分子提供了创新潜力。
