ABSTRACT
We present the application of N-difluoroacetylglucosamine (GlcNDFA) in a chemical evolution strategy to synthesize oligosaccharides. In comparison to conventional N-trifluoroacetylglucosamine, GlcNDFA exhibits superior substrate compatibility with glycosyltransferases as well as stability in aqueous environments. Using our 16-step assembly line, GlcNDFA can be used to produce homogeneous dekaparin, a heparin-like medication, with a yield of 62.2%. This underscores the significant potential of GlcNDFA as a chemical evolution precursor in the precise synthesis of structurally defined polysaccharides.
Subject(s)
Glycosyltransferases , Glycosylation , Molecular Structure , Glycosyltransferases/metabolism , Glycosyltransferases/chemistry , Hexosamines/chemistry , Hexosamines/chemical synthesis , Oligosaccharides/chemistry , Oligosaccharides/chemical synthesisABSTRACT
Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.