RESUMO
The glycosylation of natural product scaffolds with highly modified deoxysugars is often essential for their biological activity, being responsible for specific contacts to molecular targets and significantly affecting their pharmacokinetic properties. In order to provide tools for the targeted alteration of natural product glycosylation patterns, significant strides have been made to understand the biosynthesis of activated deoxysugars and their transfer. We report here efforts towards the production of plasmid-borne biosynthetic gene cassettes capable of producing TDP-activated forms of D-mycaminose, D-angolosamine and D-desosamine. We additionally describe the transfer of these deoxysugars to macrolide aglycones using the glycosyl transferases EryCIII, TylMII and AngMII, which display usefully broad substrate tolerance.
Assuntos
Glucosamina/análogos & derivados , Macrolídeos/química , Macrolídeos/metabolismo , Clonagem Molecular , Engenharia Genética , Glucosamina/química , Glucosamina/metabolismo , Estrutura Molecular , Família Multigênica/genética , Análise de Sequência , Streptomyces/química , Streptomyces/genética , Streptomyces/metabolismoRESUMO
An acetophenone containing PNA-based reagent was designed for the direct and site-specific synthesis of a cis-syn thymidine dimer lesion in genomic DNA.
Assuntos
Acetofenonas/química , DNA/síntese química , Ácidos Nucleicos Peptídicos/química , Dímeros de Pirimidina/síntese química , Acetofenonas/síntese química , Bacteriófagos/genética , Sequência de Bases , DNA/química , DNA/genética , Desoxirribonucleases de Sítio Específico do Tipo II/química , Peroxidase do Rábano Silvestre/química , Dados de Sequência Molecular , Estreptavidina/química , Especificidade por SubstratoRESUMO
PNA:DNA strands were prepared containing a flavin electron donor and a thymine dimer acceptor, which gives a strand break upon single electron reduction. With these constructs, it was confirmed that an excess electron transfer through the base stack can be efficient in an interstrand fashion. The effect of an increased distance, a changed sequence, and stacking was explored.