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. 2020 Dec 18;85(24):16157-16165.
doi: 10.1021/acs.joc.0c02134. Epub 2020 Nov 9.

A Chemoenzymatic Synthon Strategy for Synthesizing N-Acetyl Analogues of O-Acetylated N. meningitidis W Capsular Polysaccharide Oligosaccharides

Riyao Li  1 , Anoopjit S Kooner  1 , Saddam M Muthana  1   2 , Yue Yuan  1 , Hai Yu  1 , Xi Chen  1
Affiliations

A Chemoenzymatic Synthon Strategy for Synthesizing N-Acetyl Analogues of O-Acetylated N. meningitidis W Capsular Polysaccharide Oligosaccharides

Riyao Li et al. J Org Chem. .

Abstract

O-Acetylated sialic acid has been found in the Neisseria meningitidis serogroup W (NmW) capsular polysaccharide (CPS) and is a required structural component of clinically used NmW CPS-based polysaccharide and polysaccharide-conjugate vaccines. The role of sialic acid O-acetylation in NmW CPS, however, is not clearly understood. This is partially due to the lack of a precise control of the percentage and the location of O-acetylation which is labile and susceptible to migration. We explore chemoenzymatic synthetic strategies for preparing N-acetylated analogues of O-acetylated NmW CPS oligosaccharides which can serve as structurally stable probe mimics. Substrate specificity studies of NmW CPS polymerase (NmSiaDW) identified 4-azido-4-deoxy-N-acetylmannosamine (ManNAc4N3) and 6-azido-6-deoxy-N-acetylmannosamine (ManNAc6N3) as suitable chemoenzymatic synthons for synthesizing N-acetyl analogues of NmW CPS oligosaccharides containing 7-O-acetyl-N-acetylneuraminic acid (Neu5,7Ac2) and/or 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2). The synthesis was achieved by NmSiaDW-dependent sequential one-pot multienzyme (OPME) strategy with in situ generation of the corresponding sugar nucleotides from simple monosaccharides or derivatives to form N3-oligosaccharides which were converted to the desired NAc-oligosaccharides by an efficient one-step chemical transformation.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Structure of N. meningitidis serogroup W (NmW) capsular polysaccharide (CPS) containing O-acetylation at C7 or C9 of N-acetylneuraminic acid (Neu5Ac).
Scheme 1.
Scheme 1.
Schematic illustration of the reactions for one-pot two-step donor substrate specificity studies of the α2–6-sialyltransferase activity of NmSiaDW (in Step 2) using CMP-sialic acids and analogs generated in situ in Step 1.
Scheme 2.
Scheme 2.
One-pot multienzyme (OPME) chemoenzymatic systems for the formation of NmW CPS trisaccharides, tetrasaccharides, pentasaccharides, and their azido or N-acetyl analogs.
See this image and copyright information in PMC

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