Bohlin Lars, Cárdenas Paco, Backlund Anders, Göransson Ulf
Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center, Uppsala University, Box 574, 751 23, Uppsala, Sweden.
Prog Mol Subcell Biol. 2017;55:1-34. doi: 10.1007/978-3-319-51284-6_1.
Currents efforts in marine biodiscovery have essentially focused on temperate to tropical shallow water organisms. With more than 6000 species of marine plants and animals, the Kosterfjord area has the richest marine biodiversity in Swedish waters, but it remains understudied. The overall objective of our marine pharmacognosy research is to explore and reveal the pharmacological potential of organisms from this poorly explored region. More generally, we wish to understand aspects of structure-activity relationships of chemical interactions in cold-water marine environment (shallow and deep). Our strategy is based on ecologically guided search for compounds through studies of physiology and organism interactions coupled to identification of bioactive molecules guided by especially in vivo assays. The research programme originated in the beginning of the 1980s with a broad screening of Swedish marine organisms using both in vitro and in vivo assays, resulting in isolation and identification of several different bioactive molecules. Two congenerous cyclopeptides, i.e. barettin and 8,9-dihydrobarettin, were isolated from the deep-sea sponge Geodia barretti, and structurally elucidated, guided by their antifouling activity and their affinity to a selection of human serotonin receptors. To optimize the activity a number of analogues of barettin were synthezised and tested for antifouling activity. Within the EU project BlueGenics, two larger homologous peptides, barrettides A and B, were isolated from G. baretti. Also, metabolic fingerprinting combined with sponge systematics was used to further study deep-sea natural product diversity in the genus Geodia. Finally, the chemical property space model 'ChemGPS-NP' has been developed and used in our research group, enabling a more efficient use of obtained compounds and exploration of possible biological activities and targets. Another approach is the broad application of phylogenetic frameworks, which can be used in prediction of where-in which organisms-to search for novel molecules or better sources of known molecules in marine organisms. In a further perspective, the deeper understanding of evolution and development of life on Earth can also provide answers to why marine organisms produce specific molecules.
目前海洋生物发现方面的工作基本上集中在温带至热带的浅水生物上。科斯特峡湾地区拥有6000多种海洋动植物，是瑞典海域海洋生物多样性最丰富的地区，但仍未得到充分研究。我们海洋生药学研究的总体目标是探索并揭示这个未被充分探索地区生物的药理潜力。更广泛地说，我们希望了解冷水海洋环境（浅海和深海）中化学相互作用的构效关系。我们的策略基于通过生理学和生物相互作用研究进行生态导向的化合物搜索，并结合特别是体内试验来鉴定生物活性分子。该研究项目始于20世纪80年代初，通过体外和体内试验对瑞典海洋生物进行了广泛筛选，从而分离并鉴定了几种不同的生物活性分子。从深海海绵巴雷蒂地海绵中分离出两种同系环肽，即巴雷廷和8,9-二氢巴雷廷，并在其防污活性及其对一系列人类血清素受体的亲和力的指导下进行了结构解析。为了优化活性，合成了许多巴雷廷类似物并测试其防污活性。在欧盟“蓝色基因学”项目中，从巴雷蒂地海绵中分离出了两种更大的同源肽，即巴雷蒂肽A和B。此外，代谢指纹图谱结合海绵系统学被用于进一步研究地海绵属的深海天然产物多样性。最后，化学性质空间模型“ChemGPS-NP”已在我们的研究小组中开发并使用，能够更有效地利用所获得的化合物，并探索可能的生物活性和靶点。另一种方法是广泛应用系统发育框架，其可用于预测在何处——即哪种生物中——寻找海洋生物中的新分子或已知分子的更好来源。从更长远的角度来看，对地球上生命进化和发展的更深入理解也可以为海洋生物为何产生特定分子提供答案。
