RNA Duplex formation by oligodeoxynucleotides containing C-5 alkyne and C-5 thiazole substituted deoxyuridine analogs

• Published in: Tetrahedron letters Vol. 37; no. 23; pp. 3959 - 3962
• Main Authors: Gutierrez, Arnold J., Froehler, Brian C.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 03.06.1996; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ANTISENSE
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/0040-4039(96)00720-4

The binding affinity of methyl substituted C-5 propyne and C-5 thiazole ODNs for RNA was assessed by thermal denaturation analysis (Tm). The results indicate that increased size of the alkyne substituent lead to decreased affinity, but certain methyl substitutions on the thiazole lead to higher affinity complexes with RNA. The increased affinity of methylthiazole ODNs to RNA was dependent on the position of the methyl substituent with 5-methylthiazole ODN ( 2h) exhibiting the highest Tm. The 5-methylthiazole group likely increases hydrophobic interactions with adjacent base pairs in the canonical double helix. The binding affinities of methyl substituted C-5 propyne and C-5 thiazole ODNs for RNA decrease with increased size of the alkyne substituent, but certain methyl substitutions on the thiazole lead to higher affinity complexes with RNA.