摘要
黑色素瘤抑制活性（MIA）蛋白质被恶性黑素瘤细胞强烈表达和分泌，并显示出促进黑素瘤的发生和侵袭。MIA蛋白是第一个细胞外蛋白，显示在溶液中可以结合纤连蛋白III型结构域的Src同源3（SH3）结构域样折叠。与MIA一起，同源蛋白OTOR（或FDP），MIA-2和TANGO（或MIA-3）构成非胞质的蛋白质家族，除了全长TANGO和TANGO1样（TALI） - 细胞外SH3- 含有蛋白质的结构域。蛋白质家族的成员调节胶原成熟和出口，软骨发育，细胞外基质中的细胞附着和黑素瘤转移。因此，这些蛋白质可以用作针对恶性黑素瘤的药物开发的有希望的靶标。 在过去二十年中，NMR光谱已经成为药物化学中的有力技术。虽然传统的高通量筛选仅报告了低分子化合物的活性或亲和力，NMR光谱不仅涉及具有其活性的那些化合物的结构，而且还可以解开蛋白上配体结合位点的结构信息 原子分辨率。基于配体与其靶蛋白之间的相互作用的分子细节，可以更有效地进一步改进初始片段命中的结合亲和力，以产生具有显着疗效的铅结构。基于NMR的方法有望大大有助于寻求低分子量化合物，最终可以产生药物以更有效地治疗皮肤相关疾病如恶性黑素瘤。
关键词: NMR
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