An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases.
Chembiochem
; 21(10): 1412-1417, 2020 05 15.
Article
in English
| MEDLINE | ID: covidwho-832581
ABSTRACT
The structurally unique "fleximer" nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor-ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2'-deoxyribose sugars by using the N-deoxyribosyltransferaseâ
II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pentosyltransferases
/
Purine-Nucleoside Phosphorylase
/
Escherichia coli
/
Lactobacillus leichmannii
/
Nucleosides
Language:
English
Journal:
Chembiochem
Journal subject:
Biochemistry
Year:
2020
Document Type:
Article
Affiliation country:
Cbic.201900714
Similar
MEDLINE
...
LILACS
LIS