Combinatorial docking and combinatorial chemistry:: Design of potent non-peptide thrombin inhibitors
Combinatorial docking and combinatorial chemistry:: Design of potent non-peptide thrombin inhibitors
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DOI：
10.1023/a:1008040531766
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发表时间：
1999-01-01
影响因子：
3.5
通讯作者：
Weber, L
中科院分区：
文献类型：
--
作者：
Böhm, HJ;Banner, DW;Weber, L
使用计算算法自动设计可通过单步化学反应获得的新型凝血酶抑制剂。这些化合物不含酰胺键，是非手性的，分子量低于 400。在合成的 10 种化合物中，有 5 种与凝血酶结合，Ki 在纳摩尔范围内。随后对最佳化合物的凝血酶-抑制剂复合物的 X 射线结构测定 (K-i = 95 nM) 证实了预测的结合模式。这种新颖的算法适用于广泛的化学反应。
A computational algorithm was used to design automatically novel thrombin inhibitors that are available from a single-step chemical reaction. The compounds do not contain amide bonds, are achiral and have a molecular weight below 400. Of the 10 compounds that were synthesized, five bind to thrombin with a Ki in the nanomolar range. Subsequent X-ray structure determination of the thrombin-inhibitor complex for the best compound (K-i = 95 nM) confirms the predicted binding mode. The novel algorithm is applicable to a broad range of chemical reactions.