Potent small molecule mouse CD22-inhibitors: exploring the interaction of the residue at C-2 of sialic acid scaffold

Hajjaj H M Abdu-Allah; Kozo Watanabe; Koji Hayashizaki; Chiaki Takaku; Taichi Tamanaka; Hiromu Takematsu; Yasunori Kozutsumi; Takeshi Tsubata; Hideharu Ishida; Makoto Kiso

doi:10.1016/j.bmcl.2009.08.044

Potent small molecule mouse CD22-inhibitors: exploring the interaction of the residue at C-2 of sialic acid scaffold

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5573-5. doi: 10.1016/j.bmcl.2009.08.044. Epub 2009 Aug 15.

Authors

Hajjaj H M Abdu-Allah¹, Kozo Watanabe, Koji Hayashizaki, Chiaki Takaku, Taichi Tamanaka, Hiromu Takematsu, Yasunori Kozutsumi, Takeshi Tsubata, Hideharu Ishida, Makoto Kiso

Affiliation

¹ Department of Applied Bio-organic Chemistry, The United Graduate School of Agricultural Sciences, Gifu University, Gifu 501-1193, Japan. moazhajjaj@yahoo.com

PMID: 19720531
DOI: 10.1016/j.bmcl.2009.08.044

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biphenyl Compounds / chemical synthesis
Biphenyl Compounds / chemistry*
Biphenyl Compounds / pharmacology
Disaccharides / chemical synthesis
Disaccharides / chemistry*
Disaccharides / pharmacology
Mice
N-Acetylneuraminic Acid / chemistry*
Sialic Acid Binding Ig-like Lectin 2 / chemistry*
Sialic Acid Binding Ig-like Lectin 2 / metabolism

Substances

Biphenyl Compounds
Disaccharides
Sialic Acid Binding Ig-like Lectin 2
N-Acetylneuraminic Acid