Synthesis of a metallopeptide-PNA conjugate and its oxidative cross-linking to a DNA target.
A nickel(II)-PNA bioconjugate was prepared by formation of a salicylaldimine complex with the amino terminus of a peptide-PNA hybrid with the sequence Arg-His-Gly-[TACCTAGCAT]PNA-Arg-CONH2. Hybridization to complementary oligodeoxynucleotides was demonstrated, and covalent adduct formation was observed upon addition of KHSO5 as oxidant. In the absence of PNA, the reactivity of the phenolic radical generated as an intermediate was found to be G >> T >> C, A; by inclusion of the PNA delivery agent, cross-links between the two oligomers could be observed with T and C bases in the vicinity of the nickel complex, although G was still the most reactive site. The metal complex could be removed by treatment with EDTA following which the Schiff base linkage was readily hydrolyzed. The final result in this case is a salicylaldehyde moiety appended at the target site in DNA.
Kornyushyna
Olga
O
Department of Chemistry, University of Utah, 315 S. 1400 East, Salt Lake City, Utah 84112-0850, USA.
Stemmler
Ann J
AJ
Graybosch
Daina M
DM
Bergenthal
Ikuko
I
Burrows
Cynthia J
CJ
D000447:Aldehydes / Q000737:chemistry; D001483:Base Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D018736:DNA Adducts / Q000138:chemical synthesis*; D018076:DNA, Complementary / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D006868:Hydrolysis; D008956:Models, Chemical; D009532:Nickel / Q000737:chemistry; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D019800:Phenol / Q000737:chemistry; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D012545:Schiff Bases
D000447:Aldehydes; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D018076:DNA, Complementary; D016166:Free Radical Scavengers; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D020135:Peptide Nucleic Acids; D011687:Purines; D011743:Pyrimidines; D012545:Schiff Bases; C013243:salicylaldehyde; D019800:Phenol; D009532:Nickel