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Bioconjugate Chem., 12 (4), 459 -463, 2001. 10.1021/bc0100105 S1043-1802(01)00010-6
Web Release Date: June 7, 2001

Copyright 2001 American Chemical Society

Synthesis of Peptide-Oligonucleotide Conjugates for Chromium Coordination

E. R. Civitello, R. G. Leniek, K. A. Hossler, K. Haebe, and D. M. Stearns*

Department of Chemistry, Northern Arizona University, P.O. Box 5698, Flagstaff, Arizona 86011-5698

Received January 31, 2001

Revised February 28, 2001

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(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-Ala-Ser-Gly-OH and ClAc-Ser-Gly-OH, and three histidine-containing peptides, ClAc-Gly-His-Gly-OH, ClAc-Ala-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.




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