Design of bivalent ligands using hydrogen bond linkers: synthesis and evaluation of inhibitors for human beta-tryptase.
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.
Vaz
Roy J
RJ
Aventis Pharmaceuticals, 1041 Route 202/206 N, Bridgewater, NJ 088707, USA.
Gao
Zhongli
Z
Pribish
James
J
Chen
Xin
X
Levell
Julian
J
Davis
Larry
L
Albert
Eva
E
Brollo
Maurice
M
Ugolini
Antonio
A
Cramer
Dona M
DM
Cairns
Jennifer
J
Sides
Keith
K
Liu
Feng
F
Kwong
Jennifer
J
Kang
Jiesheng
J
Rebello
Sam
S
Elliot
Michael
M
Lim
Hengkeang
H
Chellaraj
Vinolia
V
Singleton
Robert W
RW
Li
Yi
Y
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
D004791:Enzyme Inhibitors; D008024:Ligands; D012697:Serine Endopeptidases; D053802:Tryptases