Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
J Enzyme Inhib Med Chem. 2009 Jun;24(3):779-94. doi: 10.1080/14756360802364401.
Macrocyclic inhibitors for the serine protease plasmin were synthesized and evaluated. The inhibitors were constructed starting from a cyclohexanone core. This core was linked to either the C- or N-terminus of a peptide so that the inhibitors were designed to interact with the non-primed or primed binding sites of the protease. Macrocycles were prepared by connecting the side chain of Tyr or Trp, via a short linker, to one end of the peptide. The activities of the macrocyclic inhibitors, while modest, were up to 10-fold more potent than a related non-cyclic analog.
合成并评价了丝氨酸蛋白酶纤溶酶的大环抑制剂。抑制剂从环己酮核心构建。该核心连接到肽的 C-或 N-末端，使抑制剂设计为与蛋白酶的非引发或引发结合位点相互作用。通过短接头将 Tyr 或 Trp 的侧链连接到肽的一端，制备大环抑制剂。大环抑制剂的活性虽然中等，但比相关的非环类似物强 10 倍。
