Hovhannisyan N, Harutyunyan Sh, Hovhannisyan A, Hambardzumyan A, Chitchyan M, Melkumyan M, Oganezova G, Avetisyan N
Institute of Biotechnology, Yerevan, Armenia.
Amino Acids. 2009 Sep;37(3):531-6. doi: 10.1007/s00726-009-0257-4. Epub 2009 Mar 27.
Thirty optically active nonprotein alpha-amino acids and peptides based thereon have been screened for their ability to interact with bovine trypsin and proteinase K from Tritirachium album Limber, which belong to the group of serine proteases. Both structure-based drug design approach and determination of enzyme activity have been used to identify low molecular weight inhibitors of trypsin and proteinase K. Compounds have been selected that according to the docking analysis were able to interact with trypsin and proteinase K. Following the docking analysis measurement of enzymes activity (2R,3S)-beta-hydroxyleucine and (2S,3R)-beta-hydroxyleucine inhibited both enzymes activity, whereas (S)-alpha-methyl-beta-phenylalanine, (R)-alpha-methyl-beta-phenylalanine, (S)-allylglycine, (R)-allylglycine, (S)-alpha-allylalanine, (R)-alpha-allylalanine and allo-O-ethylthreonine inhibited only proteinase K; and N-formyl-(S)-methionyl-(2S,3R)-hydroxyleucine, N-formyl-(S)-methionyl-(2R,3S)-hydroxyleucine, N-formyl-(S)-methionyl-(S)-allylglycine and N-formyl-(S)-methionyl-(R)-allylglycine inhibited trypsin. It has been shown that inhibition of trypsin by (2R,3S)-beta-hydroxyleucine and N-formyl-(S)-methionyl-(2R,3S)-hydroxyleucine is of a competitive mode.
已对30种旋光性非蛋白质α-氨基酸及其基于此的肽进行了筛选，以研究它们与属于丝氨酸蛋白酶组的牛胰蛋白酶和来自特异腐质霉的蛋白酶K相互作用的能力。基于结构的药物设计方法和酶活性测定都已用于鉴定胰蛋白酶和蛋白酶K的低分子量抑制剂。已选择出根据对接分析能够与胰蛋白酶和蛋白酶K相互作用的化合物。在对接分析之后进行酶活性测量，结果显示(2R,3S)-β-羟基亮氨酸和(2S,3R)-β-羟基亮氨酸抑制了两种酶的活性，而(S)-α-甲基-β-苯丙氨酸、(R)-α-甲基-β-苯丙氨酸、(S)-烯丙基甘氨酸、(R)-烯丙基甘氨酸、(S)-α-烯丙基丙氨酸、(R)-α-烯丙基丙氨酸和别-O-乙基苏氨酸仅抑制蛋白酶K；N-甲酰基-(S)-甲硫氨酰-(2S,3R)-羟基亮氨酸、N-甲酰基-(S)-甲硫氨酰-(2R,3S)-羟基亮氨酸、N-甲酰基-(S)-甲硫氨酰-(S)-烯丙基甘氨酸和N-甲酰基-(S)-甲硫氨酰-(R)-烯丙基甘氨酸抑制胰蛋白酶。已表明(2R,3S)-β-羟基亮氨酸和N-甲酰基-(S)-甲硫氨酰-(2R,3S)-羟基亮氨酸对胰蛋白酶的抑制是竞争性的。
