Abstract
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.
Acknowledgements
This research was supported by the US National Institutes of Health NIGMS (Grant R01 GM057327 to CTS).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.