Photomodulation of PS-modified oligonucleotides containing azobenzene substituent at pre-selected positions in phosphate backbone

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 24; pp. 7840 - 7849
• Main Authors: Patnaik, Satyakam, Kumar, P., Garg, B.S., Gandhi, R.P., Gupta, K.C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.12.2007; Elsevier Science
• Subjects: Analytical, structural and metabolic biochemistry; Azo Compounds - chemistry; Azobenzene; Biological and medical sciences; Circular Dichroism; E– Z photoisomerization; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods; Hybridization; Molecular Structure; Nucleic acids; p-Aminoazobenzene - analogs & derivatives; p-Aminoazobenzene - chemistry; Phosphates - chemistry; Phosphorothioate Oligonucleotides - chemistry; Photochemistry; PS-oligomers; Stereoisomerism; Thermodynamics; E– Z photoisomerization; Hybridization; PS-oligomers; Circular Dichroism; Azobenzene; Nucleotide sequence; Photoisomerization; Isomerization; Photochemical reaction; Organic thiophosphate; Oligomer; Duplex; Phosphorus Organic compounds; Circular dichroism; Azo compound; Double stranded DNA; Oligonucleotide; Chemical synthesis; E-Z photoisomerization
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.08.042

A new protocol has been developed for incorporation of photoisomerizable azobenzene substituent into synthetic PS-oligonucleotides. A new protocol has been developed for incorporation of a photoisomerizable azobenzene moiety into synthetic stereo-enriched [R p] and [S p] PS-oligonucleotides. The azobenzene pendant is attached at pre-selected positions in internucleotidic phosphorothioate oligonucleotides of both [R p] and [S p] diastereomers using a novel reagent, N-iodoacetyl- p-aminoazobenzene, 1. The modified oligomers are purified on HPLC, characterized by LC–MS, and examined for their thermal and photoisomerization properties. The azobenzene moiety imparts greater stability to oligomer duplexes in ( E) N N configuration as compared to ( Z) configuration. The placement of the azobenzene pendant close to 5′-terminus ( n − 1) and 3′-terminus of the modified PS-oligos contributes maximum stability to the duplex while a gradual decline in stability occurs with azobenzene moving toward middle of the duplex. Circular Dichroism studies reveal that the chiral environment at the phosphorus center of the PS-oligos does not alter the global conformation of the DNA duplex as such, suggesting conservation of conformation of the modified DNA strands.