Synthesis, Affinity for Complementary RNA and DNA, and Enzymatic Stability of Triazole-Linked Locked Nucleic Acids (t-LNAs).

Autor:	Kumar P; Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K., Truong L; Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K., Baker YR; Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K., El-Sagheer AH; Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.; Chemistry Branch, Department of Science and Mathematics, Faculty of Petroleum and Mining Engineering, Suez University, Suez 43721, Egypt., Brown T; Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2018 Jun 30; Vol. 3 (6), pp. 6976-6987. Date of Electronic Publication: 2018 Jun 27.
DOI:	10.1021/acsomega.8b01086
Abstrakt:	Dinucleoside phosphoramidites containing a triazole internucleotide linkage flanked by locked nucleic acid (LNA) were synthesized and incorporated into oligonucleotides (ONs). ONs bearing both LNA and triazole at multiple sites were obtained and their biophysical properties including enzymatic stability and binding affinity for RNA and DNA targets were studied. t-LNAs with four incorporations of a dinucleoside monomer having LNA on either side of the triazole linkage bind to their RNA target with significantly higher affinity and greater specificity than unmodified oligonucleotides, and are remarkably stable to nuclease degradation. A similar but reduced effect on enzymatic stability and binding affinity was noted for LNA only on the 3'-side of the triazole linkage. Thus, by combining unnatural triazole linkages and LNA in one unit (t-LNA), we produced a promising class of ONs with reduced anionic charge and potential for antisense applications. Competing Interests: The authors declare no competing financial interest.
Databáze:	MEDLINE
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