Linked Life Data

14640698

Source:http://linkedlifedata.com/resource/pubmed/id/14640698

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2003-12-3
pubmed:abstractText
MUC1 mucin is a breast cancer-associated transmembrane glycoprotein, of which the extracellular domain is formed by the repeating 20-amino acid sequence GVTSAPDTRPAPGSTAPPAH. In neoplastic breast tissue, the highly immunogenic sequence PDTRPAP (in bold above) is exposed. Antibodies raised directly against MUC1-expressing tumors offer unique access to this neoplastic state, as they represent immunologically relevant "reverse templates" of the tumor-associated mucin. In a previous study [Grinstead, J. S., et al. (2002) Biochemistry 41, 9946-9961], (1)H NMR methods were used to correlate the effects of cryptic glycosylation outside of the PDTRPAP core epitope sequence on the recognition and binding of Mab B27.29, a monoclonal antibody raised against breast tumor cells. In the study presented here, isotope-edited NMR methods, including (15)N and (13)C relaxation measurements, were used to probe the recognition and binding of the PDTRPAP epitope sequence to Fab B27.29. Two peptides were studied: a one-repeat MUC1 16mer peptide of the sequence GVTSAPDTRPAPGSTA and a two-repeat MUC1 40mer peptide of the sequence (VTSAPDTRPAPGSTAPPAHG)(2). (15)N and (13)C NMR relaxation parameters were measured for both peptides free in solution and bound to Fab B27.29. The (13)C(alpha) T(1) values best represent changes in the local correlation time of the peptide epitope upon binding antibody, and demonstrate that the PDTRPAP sequence is immobilized in the antibody-combining site. This result is also reflected in the appearance of the (15)N- and (13)C-edited HSQC spectra, where line broadening of the same peptide epitope resonances is observed. The PDTRPAP peptide epitope expands upon the peptide epitope identified previously in our group as PDTRP by homonuclear NMR experiments [Grinstead, J. S., et al. (2002) Biochemistry 41, 9946-9961], and illustrates the usefulness of the heteronuclear NMR experiments. The implications of these results are discussed within the context of MUC1 breast cancer vaccine design.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14293-305
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:14640698-Amino Acid Sequence, pubmed-meshheading:14640698-Antibodies, Monoclonal, pubmed-meshheading:14640698-Binding Sites, Antibody, pubmed-meshheading:14640698-Breast Neoplasms, pubmed-meshheading:14640698-Carbon Isotopes, pubmed-meshheading:14640698-Epitope Mapping, pubmed-meshheading:14640698-Humans, pubmed-meshheading:14640698-Immunoglobulin Fab Fragments, pubmed-meshheading:14640698-Molecular Sequence Data, pubmed-meshheading:14640698-Mucin-1, pubmed-meshheading:14640698-Nitrogen Isotopes, pubmed-meshheading:14640698-Nuclear Magnetic Resonance, Biomolecular, pubmed-meshheading:14640698-Peptide Fragments, pubmed-meshheading:14640698-Peptide Mapping, pubmed-meshheading:14640698-Protein Binding, pubmed-meshheading:14640698-Protons, pubmed-meshheading:14640698-Spectrometry, Fluorescence, pubmed-meshheading:14640698-Thermodynamics
pubmed:year
2003
pubmed:articleTitle
Epitope mapping of antigenic MUC1 peptides to breast cancer antibody fragment B27.29: a heteronuclear NMR study.
pubmed:affiliation
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington 98195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't