Issue 48, 2012

Base-pairing selectivity of a ureido-linked phenyl-2′-deoxycytidine derivative

Abstract

Incorporation of modified nucleotides into nucleic acid strands often produces conformational constraints and steric hindrances that may change the property of base pairing. In this study, we investigated a 2′-deoxycytidine derivative that tethers a phenyl moiety to the exocyclic amino group of cytosine linked through a ureido group. This derivative compound is structurally similar to the carbamoylated DNA base lesions produced in cells. The thermodynamic and structural studies showed that the modified dC formed the base pair with dG in the complementary strand, but the base-pairing selectivity toward dG was decreased under poly(ethylene glycol)-mediated osmotic stress. The phenyl group and the ureido linker attached to dC provided selectivity for the formation of base pairing exclusively with dG in a wide range of pH conditions, whereas unmodified dC stabilized the pairings with dA or dC in acidic solutions. Moreover, this modified base could not form self-pairing through intermolecular hydrogen bonds. We suggest that formation of weak pairing and protonation of the cytosine base are hindered due to the base modification. These data provide insights into the pairing selectivity of carbamoylated cytosine lesions produced in cells, and suggest applications of the 2′-deoxycytidine derivatives in medical technologies, molecular biology experiments, and synthesis of a supramolecular network of DNA strands.

Graphical abstract: Base-pairing selectivity of a ureido-linked phenyl-2′-deoxycytidine derivative

Supplementary files

Article information

Article type
Paper
Submitted
27 Sep 2012
Accepted
29 Oct 2012
First published
12 Nov 2012

Org. Biomol. Chem., 2012,10, 9664-9670

Base-pairing selectivity of a ureido-linked phenyl-2′-deoxycytidine derivative

S. Nakano, H. Oka, D. Yamaguchi, M. Fujii and N. Sugimoto, Org. Biomol. Chem., 2012, 10, 9664 DOI: 10.1039/C2OB26897C

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