title: Amino acids and peptides. LIII. Synthesis and biological activities of some pseudo-peptide analogs of PKSI-527, a plasma kallikrein selective inhibitor: the importance of the peptide backbone.
abstract: Pseudo-peptide analogs of trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-4-aminopheny l acetic acid (PKSI-527, plasma kallikrein selective inhibitor), in which an amide bond (peptide bond) has been replaced by a CH2-NH bond, i.e., trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (I), trans-4-aminomethylcyclohexanecarbonyl-psi (CH2-NH)-L-phenylalanyl-4-aminophenyl acetic acid (II) and trans-4-aminomethylcyclohexanecarbonyl-D-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (III) were synthesized. These pseudo-peptide analogs did not exhibit any detectable inhibitory activity against plasma kallikrein (PK), plasmin (PL), urokinase (UK), thrombine (TH) or trypsin (TRY). These results indicate that both carbonyl groups in the PKSI-527 are important for the manifestation of potent inhibitory activity against plasma kallikrein.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fukumizu
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuda
authors.forename: K
authors.initials: K
authors.lastname: Wanaka
authors.forename: M
authors.initials: M
authors.lastname: Tada
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
authors.forename: A
authors.initials: A
authors.lastname: Hijikata-Okunomiya
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000818:Animals; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors; D014148:Tranexamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
chemical_list: D005343:Fibrinolytic Agents; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; C064866:PKSI 527; D010649:Phenylalanine; D014148:Tranexamic Acid; D007610:Kallikreins; D010960:Plasminogen Activators; D013917:Thrombin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator