弗林蛋白酶(furin)多肽抑制剂的合成研究

Study on the design of peptide inhibitors of furin

目的以绿豆胰蛋白酶抑制剂(MBTI)Lys活性片段22肽为模板,设计能抑制弗林蛋白酶(furin)的多肽抑制剂。方法根据furin的专一性底物的特定氨基酸序列来改造设计抑制剂,用Fmoc法固相合成了两条多肽抑制剂(MBI 13和MBI 14)。结果纯化的MBI13和MBI14经HPLC和质谱鉴定合成正确,对furin的抑制常数分别为:5.6×10-7M和2.3×10-7M。结论以MBTI Lys片段为模板经过突变和优化设计,得到了较为理想的furin抑制剂,为进一步的药物设计提供依据。

Purpose Based on the 22-residue, active Lys fragment of the mung bean trpsin inhibitor, furin inhibitors were designed and synthesized. Methods Inhibitors were designed according to the consensus substrate recognition sequence of furin, and two peptide inhibitors（MBI13 and MBI14）were synthesized. Results MBI13 and MBI14 were identified by HPLC and MS, and their inhibitor constants against furin were 5.6×10^-7 M and 2.3×10^-7 M respectively. Conclusion we have demonstrated through a series of modification to the Lys fragment of MBTI that a potent furin inhibitor could be designed. Thus our result, may provide a use- ful tool for developing drug design.