Properties and Reactions of Pteridines Carrying Functionalised Side Chains at the 3-Position

Boyle, Peter; Camier, Russell

doi:10.1007/978-1-4615-2960-6_2

Cited by 2 publications

(3 citation statements)

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Section: Resultsmentioning

confidence: 99%

“…N-3 side chain pteridines 25 The key starting material for the synthesis of 2 was 2-amino-3-(3-hydroxypropyl)-6,7-diphenyl-4(3H)-pteridinone, 10. Preparation of 10 started from 5-amino-7-methylthiofurazano [3,4d]pyrimidine 4, which upon treatment with 3-chloropropanol in presence of bromine 25,26 gave 5-amino-7-(3-chloropropoxy) furazano [3,4-d]pyrimidine 5 (see Scheme 1). The proton NMR spectrum of 5 is notable for the low field signal of the -OCH 2group at d 4.67, reflecting the known very low electron density at position 7 of furazano [3,4-d]pyrimidines.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of N3- and 2-NH₂-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Crean

Camier

Lawler³

et al. 2004

Org. Biomol. Chem.

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Two 17-mer oligodeoxynucleotide-5'-linked-(6,7-diphenylpterin) conjugates, 2 and 3, were prepared as photosensitisers for targeting photooxidative damage to a 34-mer DNA oligodeoxynucleotide (ODN) fragment 1 representing the chimeric bcr-abl gene that is implicated in the pathogenesis of chronic myeloid leukaemia (CML). The base sequence in the 17-mer was 3'G G T A G T T A T T C C T T C T T5'. In the first of these ODN conjugates (2) the pterin was attached at its N3 atom, via a -(CH2)3OPO(OH)- linker, to the 5'-OH group of the ODN. Conjugate 2 was prepared from 2-amino-3-(3-hydroxypropyl)-6,7-diphenyl-4(3H)-pteridinone 10, using phosphoramidite methodology. Starting material 10 was prepared from 5-amino-7-methylthiofurazano[3,4-d]pyrimidine 4 via an unusual highly resonance stabilised cation 8, incorporating the rare 2H,6H-pyrimido[6,1-b][1,3]oxazine ring system. In the characterisation of 10 two pteridine phosphazenes, 15 and 29, were obtained, as well as new products containing two uncommon tricyclic ring systems, namely pyrimido[2,1-b]pteridine (20 and 24) and pyrimido[1,2-c]pteridine (27). In the second ODN conjugate the linker was -(CH2)5CONH(CH2)6OPO(OH)- and was attached to the 2-amino group of the pterin. In the preparation of 3, the N-hydroxysuccinimide ester 37 of 2-(5-carboxypentylamino)-6,7-diphenyl-4(3H)-pteridinone was condensed with the hexylamino-modified 17-mer. Excitation of 36 with near UV light in the presence of the single-stranded target 34-mer, 5'T G A C C A T C A A T A A G14 G A A G18 A A G21 C C C T T C A G C G G C C3' 1 caused oxidative damage at guanine bases, leading to alkali-labile sites which were monitored by polyacrylamide gel electrophoresis. Cleavage was observed at all guanine sites with a marked preference for cleavage at G14. In contrast, excitation of ODN-pteridine conjugate 2 in the presence of 1 caused oxidation of the latter predominantly at G18, with a smaller extent of cleavage at G15 and G14 (in the double-stranded portion) and G21. These results contrast with our previous observation of specific cleavage at G21 with ruthenium polypyridyl sensitisers, and suggest that a different mechanism, probably one involving Type 1 photochemical electron transfer, is operative. Much lower yields were found with the ODN-pteridine conjugate 3, perhaps as a consequence of the longer linker between the ODN and the pteridine in this case.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Synthesis of N3- and 2-NH₂-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Crean

Camier

Lawler³

et al. 2004

Org. Biomol. Chem.

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“…This fact makes relevant the effect of solar irradiation in the UV -A region on those biological systems where pterins could be accumulated. This suggestion was advanced in the last eighties (1).…”

Section: J Ntroductionmentioning

confidence: 94%

Photoinduced cleavage of plasmid DNA in the presence of pterin

et al. 2000

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The photoinduced cleavage of plasmid DNA by UV -A light in the presence of pterin was investigated. Electrophoretic analysis of the irradiated plasmid pUCI8 in the presence of pterin showed that UV light of 350 run induced the transformation of a significant proportion of the supercoiled plasmid to its relaxed form. A minor proportion of plasmid forms are also converted to the linear plasmid isomer at the longer irradiation times. All these transformations during irradiation can be observed in the absorption spectrum of DNA as function of time. Such spectral modifications correlated with the extent and the kinetics of plasmid relaxation, but not with the appearance of the linear plasmid. None of the!;e changes were operative without the irradiation with UV-A light. Control experiments with pterin or plasmid DNA irradiated separately, showed no photochemical changes. Results taken together suggest that the observed c'langes in the supercoi\ed plasmid as well as the spectral modifications both derive from the generation of single-strand break in the DNA . J ntroductionAs reported in the literature, pterins have been suspected as photoinducer of genetic alterations. The impOltance of this effect is mainly associated with the broad band absorption at wavelength larger than 320 nm . This fact makes relevant the effect of solar irradiation in the UV -A region on those biological systems where pterins could be accumulated. This suggestion was advanced in the last eighties (1).Several studies are reported in the literature describing the interaction of DNA with UV radiation. Dimers of pyrimidine are nonnal photoproducts resulting from this interaction (2). Such changes were observed in vitro and also in living organisms when DNA is exposed to UV-B (290-320 nm) radiation. Chemical changes in DNA induced by UV light result in mutagenic and carcinogenic alterations. These changes induce molecular processes competing with those involved in enzymatic reaction for repairing the DNA damage. If the later process is low enough, a genetic failure will be transmitted to the new cell (3) . It has been shown that UV-B radiation is able to induce several types of skin cancer (4).

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Properties and Reactions of Pteridines Carrying Functionalised Side Chains at the 3-Position

Cited by 2 publications

References 5 publications

Synthesis of N3- and 2-NH₂-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Synthesis of N3- and 2-NH₂-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Photoinduced cleavage of plasmid DNA in the presence of pterin

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Properties and Reactions of Pteridines Carrying Functionalised Side Chains at the 3-Position

Cited by 2 publications

References 5 publications

Synthesis of N3- and 2-NH2-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Synthesis of N3- and 2-NH2-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Photoinduced cleavage of plasmid DNA in the presence of pterin

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Synthesis of N3- and 2-NH₂-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene

Synthesis of N3- and 2-NH₂-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr–abl chimeric gene