Marine-derived microbes and molecules for drug discovery.
Marine-derived microbes and molecules for drug discovery.
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DOI：
10.1186/s41232-022-00207-9
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发表时间：
2022-06-03
影响因子：
8.1
通讯作者：
中科院分区：
文献类型：
--
作者：
作为自身免疫性疾病治疗来源的海洋生物分子受到越来越多的关注。长崎县岛屿众多，四面环海、海峡、湾湾、海湾、海湾，海岸线长度仅次于北海道，是日本第二长的县。我们收集了超过20,000种海洋微生物，并一直在准备一个原始的海洋微生物提取物库，其中包含中小型生物分子，这些生物分子可能会穿透细胞膜并干扰细胞内蛋白质-蛋白质相互作用，从而参与家族性地中海热等自身炎症性疾病的发展。此外，我们一直在开发室内鲨鱼养殖系统，以制备鲨鱼纳米抗体，这些纳米抗体可以开发为自身免疫性疾病的潜在治疗剂。鲨鱼产生重链抗体，称为免疫球蛋白新抗原受体（IgNAR），由一个可变结构域（VNAR）和五个恒定结构域（CNAR）组成；其中，VNAR可以识别多种外来抗原。 VNAR 单结构域片段（称为纳米抗体）可以在大肠杆菌中表达，并且具有自身免疫性疾病理想治疗候选物的特性。鲨鱼纳米抗体含有互补决定区，这些区域是通过可变、多样性和连接片段的体细胞重排、片段末端修剪以及 N 和 P 添加而形成的，正如在哺乳动物抗体的可变结构域中发现的那样。因此，鲨鱼纳米抗体的亲和力和多样性预计可与哺乳动物抗体相媲美。此外，鲨鱼纳米抗体物理性能稳定，制备成本低廉。因此，它们可能会在未来导致高度特异性、稳定、有效和廉价的生物治疗药物的开发。在这篇综述中，我们首先总结了治疗自身免疫性疾病的常规小分子药物和单克隆抗体疗法的发展历史，然后介绍了我们在长崎大学的药物发现系统，包括原始海洋微生物提取物库的制备和鲨鱼纳米抗体的开发。在线版本包含可在 10.1186/s41232-022-00207-9 获取的补充材料。
Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein–protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies. The online version contains supplementary material available at 10.1186/s41232-022-00207-9.
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影响因子：
27.4
作者：
HENCH, PS;KENDALL, EC;POLLEY, HF
通讯作者：
POLLEY, HF
影响因子：
5.6
作者：
Chen, Ya;de Lomana, Marina Garcia;Kirchmair, Johannes
通讯作者：
Kirchmair, Johannes
DOI：
10.1073/pnas.1321502111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Feige, Matthias J.;Graewert, Melissa A.;Buchner, Johannes
通讯作者：
Buchner, Johannes
影响因子：
5.8
作者：
Glaser, Keith B.;Mayer, Alejandro M. S.
通讯作者：
Mayer, Alejandro M. S.
影响因子：
5
作者：
Harapas, Cassandra R.;Steine, Annemarie;Masters, Seth L.
通讯作者：
Masters, Seth L.