Synthesis of peptide-oligonucleotide conjugates for chromium coordination.
The synthesis of the first peptide-oligonucleotide conjugate designed to coordinate chromium(III) is reported. The overall goal of this work is to synthesize di-deoxynucleotides tethered with chromium(III)-coordinating appendages to model chromium-DNA-protein cross-links, which are a type of DNA lesion that may be involved in chromium-induced cancers. The conjugate dGp(NHCH(2)CH(2)S-Ac-Gly-Ser-Gly-OH)G was made by coupling the peptide, ClAc-Gly-Ser-Gly-OH, and dinucleotide, dGp(NHCH(2)CH(2)SH)G, through a thioether moiety. The conjugate was characterized by HPLC and mass spectrometry. Previously reported methods for small-scale solid-phase synthesis of peptides and dinucleotide were unsuitable; therefore, gram-scale solution-phase methods were developed. We also report the gram-scale syntheses of two other serine-containing peptides, ClAc-betaAla-Ser-Gly-OH and ClAc-Ser-Gly-OH, and three histidine-containing peptides, ClAc-Gly-His-Gly-OH, ClAc-betaAla-His-Gly-OH, and ClAc-His-Gly-OH. The synthesis and characterization of chromium-containing peptide-oligonucleotide conjugates will ultimately help us to understand chromium-DNA interactions at a molecular level, which is necessary before we can determine how chromium causes cancer.
Civitello
E R
ER
Department of Chemistry, Northern Arizona University, P.O. Box 5698, Flagstaff, Arizona 86011-5698, USA.
Leniek
R G
RG
Hossler
K A
KA
Haebe
K
K
Stearns
D M
DM
D002857:Chromium / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects; D006639:Histidine / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis*; D010455:Peptides / Q000138:chemical synthesis*; D011506:Proteins / Q000737:chemistry; D012694:Serine / Q000737:chemistry
D003432:Cross-Linking Reagents; D009841:Oligonucleotides; D010455:Peptides; D011506:Proteins; D002857:Chromium; D012694:Serine; D006639:Histidine; D004247:DNA