Cg Base Pair Recognition Within Dna Triple Helices Using N-Methyl-3H-Pyrrolo[2,3-d]Pyrimidin-2(7H)-One Nucleoside Analogues

Abstract

Triplex-mediated recognition of Py.Pu base pairs in DNA is a greater challenge than for Pu.Py base pairs as fewer hydrogen bonds are presented for binding in the major groove. Initial studies on m-aminophenyl-modified analogues of the bicyclic nucleoside N-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7 H)-one suggest that selective recognition of the CG base pair is possible.

Keywords:

• Triple helices
• CG recognition
• triplex
• fluorescence melting
• UV melting

This work was funded by BBSRC and Cancer Research UK. All oligonucleotides were synthesized by ATDBio Ltd. (www.atdbio.com).

Notes

^a C = 5-methyl-2′-deoxycytidine.

^mC = 5-methyl-2′-deoxycytidine.

^b MALDI-TOF MS of modified TFO: X = ^APP found m/z 4612.0 (expected 4611.2).

^a C = 5-methylcytidine, P = propargylamino-dU, D = DABCYL (fluorescence quencher), F = FAM (fluorescent marker).

^mC = 5-methylcytidine, P = propargylamino-dU, D = DABCYL (fluorescence quencher), F = FAM (fluorescent marker).

^b MALDI-TOF MS of modified TFO: X = ^MP found m/z 5807.4 [M+H]⁺ (expected 5806.1), X = ^APP found m/z 5884.7 [M+H]⁺ (expected 5884.2), X = ^AAPP found m/z 5926.7 [M+H]⁺ (expected 5926.3), X = ^UPP found m/z 5927.3 [M+H]⁺ (expected 5927.3).