期刊
ACS CHEMICAL BIOLOGY
卷 17, 期 5, 页码 1207-1214出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.2c00146
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资金
- NIH [HL094463, HL144970, GM123792, GM134738, HL158932]
- Eshelman Innovation Institute
- GlycoMIP, a National Science Foundation Materials Innovation Platform [DMR-1933525]
A library of structurally homogeneous HS and CS chimeric dodecasaccharides (12-mers) has been synthesized using natural biosynthetic enzymes. These chimeras exhibit anticoagulant activity and can be reversibly neutralized by protamine, offering a new class of glycan molecules for biological research.
Heparan sulfate (HS) and chondroitin sulfate (CS) are two structurally distinct natural polysaccharides. Here, wereport the synthesis of a library of seven structurally homogeneous HS and CS chimeric dodecasaccharides (12-mers). The synthesiswas accomplished using six HS biosynthetic enzymes and four CS biosynthetic enzymes. The chimeras contain a CS domain on thereducing end and a HS domain on the nonreducing end. The synthesized chimeras display anticoagulant activity as measured byboth in vitro and ex vivo experiments. Furthermore, the anticoagulant activity ofH/C 12-mer 5is reversible by protamine, a U.S.Food and Drug Administration-approved polypeptide to neutralize anticoagulant drug heparin. Ourfindings demonstrate thesynthesis of unnatural HS-CS chimeric oligosaccharides using natural biosynthetic enzymes, offering a new class of glycan moleculesfor biological research.
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