title: Macrocyclic inhibitors for the serine protease plasmin.
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.
authors.affiliation: Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Fengtian
authors.initials: F
authors.lastname: Xue
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Seto
mesh_terms: D001665:Binding Sites; D003512:Cyclohexanones / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005341:Fibrinolysin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D003512:Cyclohexanones; D047028:Macrocyclic Compounds; D010455:Peptides; D015842:Serine Proteinase Inhibitors; D014443:Tyrosine; C036468:cyclohexanone; D014364:Tryptophan; D005341:Fibrinolysin