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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jul 1;88(13):5602–5606. doi: 10.1073/pnas.88.13.5602

Sequence-specific photo-induced cross-linking of the two strands of double-helical DNA by a psoralen covalently linked to a triple helix-forming oligonucleotide.

M Takasugi 1, A Guendouz 1, M Chassignol 1, J L Decout 1, J Lhomme 1, N T Thuong 1, C Hélène 1
PMCID: PMC51925  PMID: 2062839

Abstract

On the basis of the structure of DNA-psoralen bis adducts (formed by psoralen with two thymines on opposite strands), a psoralen-oligonucleotide conjugate was designed to photoinduce a cross-link between the two DNA strands at a specific sequence. Psoralen was attached via its C-5 position to a 5'-thiophosphate group of an 11-mer homopyrimidine oligonucleotide. The 11-mer binds to an 11-base-pair homopurine.homopyrimidine sequence of a DNA fragment, where it forms a triple helix. Upon near-UV-irradiation, the two strands of DNA are crosslinked at the TpA step present at the triplex-duplex junction. The reaction is specific for the homopurine.homopyrimidine DNA sequence and requires both oligonucleotide recognition of the DNA major groove and intercalation of psoralen at the triplex-duplex junction. The yield of the photo-induced cross-linking reaction is quite high (greater than 80%). Such psoralen-oligonucleotide conjugates are probes of sequence-specific triple-helix formation and could be used to selectively control gene expression or to induce site-directed mutations.

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Selected References

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