Synthesis of biotinylated chondroitin sulfate DA and AD tetrasaccharides composed of hetero-type disaccharide units, and their interactions with the mAb MO-225. (1st March 2023)

• Record Type: Journal Article
• Authors: Uemura, Asumi; Nadanaka, Satomi; Kitagawa, Hiroshi; Tamura, Jun-ichi
• Is Part Of: Bioorganic & medicinal chemistry. Volume 81(2023)
• Publication Date: 2023-03-01
• Subjects: Chondroitin sulfate -- Glycosylation -- Oligosaccharide synthesis -- mAb MO-225; All allyl -- Alloc allyloxycarbonyl -- BAIB iodobenzene diacetate -- CS chondroitin sulfate -- CSA (+)-10-camphorsulfonic acid -- DMAP N, N-dimethylaminopyridine -- GlcA d-glucuronic acid -- GalNAc N-acetyl-d-galactosamine -- Lev levulinoyl -- mAb monoclonal antibody -- MBz 4-methylbenzoyl -- Piv pivaloyl -- TBDMS tert-butyldimethylsilyl -- TBDPS tert-butyldiphenylsilyl -- TEMPO 2, 2, 6, 6-tetramethyl-1-piperidinyloxy radical -- TMSOTf trimethylsilyl triflate -- Troc 2, 2, 2-trichloroethoxycarbonyl -- Z benzyloxycarbonyl; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2023.117191
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Monoclonal antibody MO-225 bound more strongly to chondroitin sulfate repeating tetrasaccharide DA-type than DD- and AD types. Highlights: β-Selective glycosylation with 2-azide-type galactosyl donor. Stereoselective synthesis of chondroitin sulfate tetrasaccharide. Regioselective O -sulfation to form hetero-type chondroitin sulfate dimer. DA-type tetrasaccharide strongly interacts with MO-224 than DD and AD-type. Abstract: Chondroitin sulfate (CS), a linear acidic polysaccharide, exhibits numerous biological activities that are dependent on sulfation patterns. CS oligosaccharides comprise repeating disaccharide units with different (hetero)-type sulfation patterns and are common in nature. We herein report the synthesis of the following biotinylated CS tetrasaccharides: CS-AD [βGalNAc4S(1–4)βGlcA(1–3)βGalNAc6S(1–4)βGlcA2S] and CS-DA [βGalNAc6S(1–4)βGlcA2S(1–3)βGalNAc4S(1–4)βGlcA], in a stereo-controlled manner. We also demonstrated that the CS-d -specific monoclonal antibody MO-225 bound more strongly to CS-DA than to CS-DD or -AD.