Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16)

Title:
Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16)
Authors:
Whelan, Rebecca J. ( 0000-0002-9293-1528 ) ; Berman, Zach T.; Moore, Lee J.; Knudson, Kathleen E.
Abstract:
A highly conserved region of 21 amino acids flanked by cysteine residues, contained within a larger repeated domain, has been proposed to be the antibody-binding site in the ovarian cancer biomarker CA125 (MUC16). In this study solid-phase peptide synthesis with Fmoc protection chemistry was used to assemble a 21-mer peptide corresponding to the most frequently occurring antibody binding sequence in CA125. Potentially significant sequence variants were also synthesized. Peptide secondary structure was investigated using Fourier transform infrared spectroscopy, revealing the consensus sequence peptide to be largely unstructured at physiological pH whether the cysteine residues were reduced or were oxidized to form an intramolecular disulfide bond. Substitution of serine for proline at position 8 (P8S) results in β-sheet formation in peptides involved in intramolecular disulfide bonds. This β-sheet structure does not persist in peptides incapable of intramolecular disulfide bonding because of sequence nor in peptides treated with the reducing agent dithiothreitol. In CA125, P8S is predicted to occur in ~25% of repeat domains, suggesting that this structural motif is a non-negligible contributor to overall structure and function. These findings suggest that future structural characterization efforts of CA125 should be especially mindful of the amino acid sequence and oxidation state of the protein.
Citation:
Berman, Zach T., Moore, Lee J., Knudson, Kathleen E., and Rebecca J. Whelan. 2010. Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16). Tumor Biology 31:495-502.
Publisher:
Springer Verlag for International Society of Oncology and BioMarkers
DATE ISSUED:
2010-10
Department:
Chemistry
Type:
article
PUBLISHED VERSION:
10.1007/s13277-010-0062-4
PERMANENT LINK:
http://hdl.handle.net/11282/309890

Full metadata record

DC FieldValue Language
dc.contributor.authorWhelan, Rebecca J.en_US
dc.contributor.authorBerman, Zach T.en_US
dc.contributor.authorMoore, Lee J.en_US
dc.contributor.authorKnudson, Kathleen E.en_US
dc.date.accessioned2013-12-23T16:20:26Zen
dc.date.available2013-12-23T16:20:26Zen
dc.date.issued2010-10en
dc.identifier.citationBerman, Zach T., Moore, Lee J., Knudson, Kathleen E., and Rebecca J. Whelan. 2010. Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16). Tumor Biology 31:495-502.en_US
dc.identifier.issn1010-4283en_US
dc.identifier.urihttp://hdl.handle.net/11282/309890en
dc.description.abstractA highly conserved region of 21 amino acids flanked by cysteine residues, contained within a larger repeated domain, has been proposed to be the antibody-binding site in the ovarian cancer biomarker CA125 (MUC16). In this study solid-phase peptide synthesis with Fmoc protection chemistry was used to assemble a 21-mer peptide corresponding to the most frequently occurring antibody binding sequence in CA125. Potentially significant sequence variants were also synthesized. Peptide secondary structure was investigated using Fourier transform infrared spectroscopy, revealing the consensus sequence peptide to be largely unstructured at physiological pH whether the cysteine residues were reduced or were oxidized to form an intramolecular disulfide bond. Substitution of serine for proline at position 8 (P8S) results in β-sheet formation in peptides involved in intramolecular disulfide bonds. This β-sheet structure does not persist in peptides incapable of intramolecular disulfide bonding because of sequence nor in peptides treated with the reducing agent dithiothreitol. In CA125, P8S is predicted to occur in ~25% of repeat domains, suggesting that this structural motif is a non-negligible contributor to overall structure and function. These findings suggest that future structural characterization efforts of CA125 should be especially mindful of the amino acid sequence and oxidation state of the protein.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Verlag for International Society of Oncology and BioMarkersen_US
dc.identifier.doi10.1007/s13277-010-0062-4en
dc.subject.departmentChemistryen_US
dc.titleSynthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16)en_US
dc.typearticleen_US
dc.identifier.journalTumor Biologyen_US
dc.subject.keywordBioanalytical spectroscopyen_US
dc.subject.keywordCA125en_US
dc.subject.keywordMUC16en_US
dc.subject.keywordOvarian canceren_US
dc.subject.keywordBiomarkeren_US
dc.subject.keywordSynthetic peptideen_US
dc.subject.keywordRepeat domainen_US
dc.subject.keywordEpitopeen_US
dc.subject.keywordInfrared spectroscopyen_US
dc.subject.keywordInfrared spectroscopyen_US
dc.subject.keywordFTIRen_US
All Items in The Five Colleges of Ohio Digital Repository are protected by copyright, with all rights reserved, unless otherwise indicated.