Incorporating uracil and 5-halouracils into short peptide nucleic acids for enhanced recognition of A-U pairs in dsRNAs

Nucleic Acids Research
Kiran M PatilGang Chen

Abstract

Double-stranded RNA (dsRNA) structures form triplexes and RNA-protein complexes through binding to single-stranded RNA (ssRNA) regions and proteins, respectively, for diverse biological functions. Hence, targeting dsRNAs through major-groove triplex formation is a promising strategy for the development of chemical probes and potential therapeutics. Short (e.g., 6-10 mer) chemically-modified Peptide Nucleic Acids (PNAs) have been developed that bind to dsRNAs sequence specifically at physiological conditions. For example, a PNA incorporating a modified base thio-pseudoisocytosine (L) has an enhanced recognition of a G-C pair in an RNA duplex through major-groove L·G-C base triple formation at physiological pH, with reduced pH dependence as observed for C+·G-C base triple formation. Currently, an unmodified T base is often incorporated into PNAs to recognize a Watson-Crick A-U pair through major-groove T·A-U base triple formation. A substitution of the 5-methyl group in T by hydrogen and halogen atoms (F, Cl, Br, and I) causes a decrease of the pKa of N3 nitrogen atom, which may result in improved hydrogen bonding in addition to enhanced base stacking interactions. Here, we synthesized a series of PNAs incorporating uracil and ha...Continue Reading

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Citations

Feb 13, 2019·Chemistry : a European Journal·Venubabu KotikamEriks Rozners
Sep 25, 2020·Biopolymers·Shiqin MiaoDennis Bong
Aug 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alan Ann Lerk OngGang Chen
Jun 16, 2021·Biopolymers·J Dinithi R PereraPeter M Glazer
Sep 21, 2019·The Journal of Organic Chemistry·Ilze KumpinaEriks Rozners
Aug 10, 2021·Beilstein Journal of Organic Chemistry·Nikita BrodyaginEriks Rozners

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Methods Mentioned

BETA
column chromatography
NMR

Software Mentioned

Discovery Studio
GROMACS
Discovery
Gaussian

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