The Kitasato Institute, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University. Japan.
Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(2):85-102. doi: 10.2183/pjab.86.85.
Chitin, the second most abundant polysaccharide in nature, occurs in fungi, some algae and many invertebrates, including insects. Thus, chitin synthesis and degradation could represent specific targets for fungicides and insecticides. Chitinases hydrolyze chitin into oligomers of N-acetyl-D-glucosamine at key points in the life cycles of organisms, consequently, chitinase inhibitors have become subject of increasing interest. This review covers the development of two chitinase inhibitors of natural origin, Argifin and Argadin, isolated from the cultured broth of microorganisms in our laboratory. In particular, the practical total synthesis of these natural products, the synthesis of lead compounds via computer-aided rational molecular design, and discovery methods that generate only highly-active compounds using a kinetic target(chitinase)-guided synthesis approach (termed in situ click chemistry) are described.
几丁质是自然界中第二丰富的多糖，存在于真菌、一些藻类和许多无脊椎动物中，包括昆虫。因此，几丁质的合成和降解可能是杀菌剂和杀虫剂的特定目标。几丁质酶在生物体的生命周期的关键点上将几丁质水解成 N-乙酰-D-葡萄糖胺的低聚物，因此，几丁质酶抑制剂已成为越来越多的关注的对象。这篇综述涵盖了两种天然来源的几丁质酶抑制剂 Argifin 和 Argadin 的开发，它们是从我们实验室培养的微生物培养液中分离得到的。特别是，这些天然产物的实际全合成、通过计算机辅助合理分子设计合成先导化合物的方法以及仅使用动力学靶标（几丁质酶）指导合成方法（称为原位点击化学）生成高活性化合物的发现方法都进行了描述。
