title: Synthesis and biological evaluation of novel irreversible serine protease inhibitors using amino acid based sulfonyl fluorides as an electrophilic trap.
abstract: We have designed and synthesized novel irreversible serine protease inhibitors containing aliphatic sulfonyl fluorides as an electrophilic trap. These substituted taurine sulfonyl fluorides derived from taurine or protected amino acids were conveniently synthesized from β-aminoethanesulfonyl chlorides using KF/18-crown-6 or from β-aminoethanesulfonates using DAST. Their potency of irreversible inhibition of serine proteases is described in different enzyme assays using chymotrypsin leading to binding affinities up to 22 μM.
authors.affiliation: Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Arwin J
authors.initials: AJ
authors.lastname: Brouwer
authors.forename: Tarik
authors.initials: T
authors.lastname: Ceylan
authors.forename: Anika M
authors.initials: AM
authors.lastname: Jonker
authors.forename: Tima
authors.initials: T
authors.lastname: van der Linden
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D007700:Kinetics; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013441:Sulfinic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013654:Taurine / Q000031:analogs & derivatives
chemical_list: D000596:Amino Acids; D015842:Serine Proteinase Inhibitors; D013441:Sulfinic Acids; D013654:Taurine; C048899:sulfuryl fluoride; D002918:Chymotrypsin