Synthesis and Evaluation of New Spacers for Use as dsDNA End-Caps

• Published in: Bioconjugate chemistry Vol. 21; no. 8; pp. 1545 - 1553
• Main Authors: Ng, Pei-Sze, Laing, Brian M, Balasundarum, Ganesan, Pingle, Maneesh, Friedman, Alan, Bergstrom, Donald E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.08.2010
• Subjects: Amides - chemistry; Chemistry; Deoxyribonucleic acid; DNA; DNA - chemistry; Ethylene Glycols - chemistry; Molecules; Naphthalene; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Organophosphorus Compounds - chemistry; Temperature; Thiophenes - chemistry; Transition Temperature
• ISSN: 1043-1802; 1520-4812; 1520-4812
• DOI: 10.1021/bc100202y

A series of aliphatic and aromatic spacer molecules designed to cap the ends of DNA duplexes have been synthesized. The spacers were converted into dimethoxytrityl-protected phosphoramidites as synthons for oligonucleotides synthesis. The effect of the spacers on the stability of short DNA duplexes was assessed by melting temperature studies. End-caps containing amide groups were found to be less stabilizing than the hexaethylene glycol spacer. End-caps containing either a terthiophene or a naphthalene tetracarboxylic acid diimide were found to be significantly more stabilizing. The former showed a preference for stacking above an A•T base pair. Spacers containing only methylene (−CH2−) and amide (−CONH−) groups interact weakly with DNA and consequently may be optimal for applications that require minimal influence on DNA structure but require a way to hold the ends of double-stranded DNA together.