Synthesis and biological validation of N7-(4-chlorophenoxyethyl) substituted dinucleotide cap analogs for mRNA translation.
Bioorg Med Chem
; 21(15): 4570-4, 2013 Aug 01.
Article
de En
| MEDLINE
| ID: mdl-23777824
ABSTRACT
Design, synthesis and biological validation of dinucleotide cap analogs, N(7)-(4-chlorophenoxyethyl)-G(5')ppp(5')G (5a) and N(7)-(4-chlorophenoxyethyl)-m(3'-O)G(5')ppp(5')G (5b) are reported. The effect of N(7)-(4-chlorophenoxyethyl) substitution on cap analogs has been evaluated with respect to its in vitro transcription by using T7 RNA polymerase capping efficiency, and translational activity. The gel shift assay indicates that the new cap analogs (5a, 5b) showed 77% and 76% capping efficiency respectively, whereas the standard cap analog, m(7)G(5')ppp(5')G has a capping efficiency of 63%. The capping efficiency experiment clearly demonstrates that the N(7)-modified analogs are good substrate for T7 RNA polymerase. It is noteworthy that the mRNA poly(A) capped with N(7)-(4-chlorophenoxyethyl)-m(3'-O)G(5')ppp(5')G (5b) was translated â¼1.64-fold more efficiently, while compound (5a) was translated â¼0.72-fold less efficiently than mRNA capped with standard cap analog. The observed low translation activity for (5a) could be due to stability in the form of dinucleotide cap analogs. Based on the substrate compatability of the N(7) modification in dinucleotide form, these new analogs may be used for structure function studies as well as protein production.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Analogues des coiffes des ARN
/
ARN messager
Limites:
Humans
Langue:
En
Journal:
Bioorg Med Chem
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2013
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique