title: Design of bivalent ligands using hydrogen bond linkers: synthesis and evaluation of inhibitors for human beta-tryptase.
abstract: We exploit the concept of using hydrogen bonds to link multiple ligands for maintaining simultaneous interactions with polyvalent binding sites. This approach is demonstrated by the syntheses and evaluation of pseudo-bivalent ligands as potent inhibitors of human beta-tryptase.
authors.affiliation: Aventis Pharmaceuticals, 1041 Route 202/206 N, Bridgewater, NJ 088707, USA.
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Vaz
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Gao
authors.forename: James
authors.initials: J
authors.lastname: Pribish
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Julian
authors.initials: J
authors.lastname: Levell
authors.forename: Larry
authors.initials: L
authors.lastname: Davis
authors.forename: Eva
authors.initials: E
authors.lastname: Albert
authors.forename: Maurice
authors.initials: M
authors.lastname: Brollo
authors.forename: Antonio
authors.initials: A
authors.lastname: Ugolini
authors.forename: Dona M
authors.initials: DM
authors.lastname: Cramer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cairns
authors.forename: Keith
authors.initials: K
authors.lastname: Sides
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kwong
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Kang
authors.forename: Sam
authors.initials: S
authors.lastname: Rebello
authors.forename: Michael
authors.initials: M
authors.lastname: Elliot
authors.forename: Hengkeang
authors.initials: H
authors.lastname: Lim
authors.forename: Vinolia
authors.initials: V
authors.lastname: Chellaraj
authors.forename: Robert W
authors.initials: RW
authors.lastname: Singleton
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D008970:Molecular Weight; D012697:Serine Endopeptidases / Q000187:drug effects*; D013329:Structure-Activity Relationship; D053802:Tryptases
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D012697:Serine Endopeptidases; D053802:Tryptases