Potent small molecule mouse CD22-inhibitors: exploring the interaction of the residue at C-2 of sialic acid scaffold.
Our previous study revealed that compound 1 (9-(4'-hydroxy-4-biphenyl)acetamido-9-deoxy-Neu5Gcalpha2-6GalOMP) has the most promising affinity for mCD22. Replacing the subterminal galactose residue of 1 with benzyl or biphenylmethyl as aglycone led to 38- and 20-fold higher potency, respectively. This discovery represents a new direction in inhibitor design suitable for pharmaceutical development.
Abdu-Allah
Hajjaj H M
HH
Department of Applied Bio-organic Chemistry, The United Graduate School of Agricultural Sciences, Gifu University, Gifu 501-1193, Japan. moazhajjaj@yahoo.com
Watanabe
Kozo
K
Hayashizaki
Koji
K
Takaku
Chiaki
C
Tamanaka
Taichi
T
Takematsu
Hiromu
H
Kozutsumi
Yasunori
Y
Tsubata
Takeshi
T
Ishida
Hideharu
H
Kiso
Makoto
M
D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry* / Q000378:metabolism
D001713:Biphenyl Compounds; D004187:Disaccharides; D051918:Sialic Acid Binding Ig-like Lectin 2; D019158:N-Acetylneuraminic Acid