Photo-cross-linking of psoralen derivatized oligonucleoside methylphosphonates to single-stranded DNA

Abstract

The preparation of oligodeoxyribonucleoside methylphosphonates derivatized with 3-[(2-aminoethyl)carbamoyl]psoralen [(ae)CP] is described. These derivatized oligomers are capable of cross-linking with single-stranded DNA via formation of a photoadduct between the furan side of the psoralen ring and a thymidine of the target DNA when the oligomer-target duplex is irradiated with 365-nm light. The photoreactions of (ae)CP-derivatized methylphosphonate oligomers with single-stranded DNA targets in which the position of the psoralen-linking site is varied are characterized and compared to results obtained with oligomers derivatized with 4'-[[N-(aminoethyl)amino]methyl]-4,5',8-trimethylpsoralen [(ae)AMT]. It appears that the psoralen ring can stack on the terminal base pair formed between the oligomer and its target DNA or can intercalate between the last two base pairs of the oligomer-target duplex. Oligomers derivatized with (ae)CP cross-link efficiently to a thymidine located in the last base pair (n position) or 3' to the last base pair (n + 1 position) of the target, whereas the (ae)AMT-derivatized oligomers cross-link most efficiently to a thymidine located in the n + 1 position. The results show that both the extent and kinetics of cross-linking are influenced by the location of the psoralen-linking site in the oligomer-target duplex.

Programmed Materials Synthesis with DNA

“…However, there is an intense parallel research effort focused on the modification of oligonucleotide properties, which may allow one to circumvent some of these limitations. , One way to increase the stability of these materials could be through a post-cross-linking reaction. Modified DNA with cross-linkable groups such as stilbene already exist and can be easily implemented in the nanoparticle programmed assembly methods described herein. − In addition, the use of peptide nucleic acids, which have a higher affinity for oligonucleotides and can be used under less stringent conditions (lower temperatures and salt concentrations), also may offer a way to overcome some of the aforementioned limitations. Nevertheless, this is a new and very powerful tool for organizing nanoparticle building blocks into extended, functional two- and three-dimensional structures.…”

Site-specific and photo-induced alkylation of DNA by a dimethylanthraquinone-oligodeoxynucleotide conjugate

“…Related naphthoquinone conjugates did not exhibit this activity and covalent attachment of a naphthoquinone had no effect on duplex hybridization (12). Interestingly, psoralen intercalates into duplex DNA, but it does not seem to stabilize hybridization when linked as a oligodeoxynucleotide-psoralen conjugate (7,(34)(35)(36). …”

“…The nucleotide directly adjacent to the duplex was also varied in anticipation of its key role in modification. This site had been the sole target of alkylation in a related methylnaphthoquinone system (12) and dominated photocyclization in certain psoralen-based systems (35). Similar to psoralen and naphthoquinone, anthraquinone absorbs near UV light (340-360 nm), which allows for its selective activation in the presence of DNA.…”

A new class of Ru(ii) polyazine agents with potential for photodynamic therapy

“…9b, 11a,b Samples treated with complex 3 also exhibited a higher degree of smearing of the lower band, which is attributed to the steric constraints from the two-anthryl units which could enhance crosslinking of DNA through the formation of multiple photoadducts by a single Ru(II) complex. 11c, 12 These results strongly suggest that the anthracene-[Ru]-dpp hybrid systems uniquely modify plasmid DNA via an 3 O 2 -independent mechanism attributed to the appended anthryl unit(s).…”