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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 les...

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Bibliographic Details
Published in:Bioconjugate chemistry 2001-07, Vol.12 (4), p.459-463
Main Authors: Civitello, E. R, Leniek, R. G, Hossler, K. A, Haebe, K, Stearns, D. M
Format: Article
Language:English
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Summary: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(NHCH2CH2S-Ac-Gly-Ser-Gly-OH)G was made by coupling the peptide, ClAc-Gly-Ser-Gly-OH, and dinucleotide, dGp(NHCH2CH2SH)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-βAla-Ser-Gly-OH and ClAc-Ser-Gly-OH, and three histidine-containing peptides, ClAc-Gly-His-Gly-OH, ClAc-βAla-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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc0100105