Synthesis of peptide-oligonucleotide conjugates for chromium coordination

Edgar R Civitello, R. G. Leniek, K. A. Hossler, K. Haebe, Diane M Stearns

Research output: Contribution to journalArticle

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Abstract

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(NHCH2-CH2SH)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, C1Ac-βAla-Ser-Gly-OH and C1Ac-Ser-Gly-OH, and three histidine-containing peptides, C1Ac-Gly-His-Gly-OH, C1Ac-βAla-His-Gly-OH, and C1Ac-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.

Original languageEnglish (US)
Pages (from-to)459-463
Number of pages5
JournalBioconjugate Chemistry
Volume12
Issue number4
DOIs
StatePublished - 2001

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Oligonucleotides
Chromium
Peptides
DNA
alanyl-seryl-glycine
glycyl-histidyl-glycine
histidylglycine
Solid-Phase Synthesis Techniques
Sulfides
Histidine
Serine
Mass spectrometry
Mass Spectrometry
Neoplasms
High Pressure Liquid Chromatography
Proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Synthesis of peptide-oligonucleotide conjugates for chromium coordination. / Civitello, Edgar R; Leniek, R. G.; Hossler, K. A.; Haebe, K.; Stearns, Diane M.

In: Bioconjugate Chemistry, Vol. 12, No. 4, 2001, p. 459-463.

Research output: Contribution to journalArticle

Civitello, Edgar R ; Leniek, R. G. ; Hossler, K. A. ; Haebe, K. ; Stearns, Diane M. / Synthesis of peptide-oligonucleotide conjugates for chromium coordination. In: Bioconjugate Chemistry. 2001 ; Vol. 12, No. 4. pp. 459-463.
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