Linked Life Data

16482104

Source:http://linkedlifedata.com/resource/pubmed/id/16482104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-3-23
pubmed:abstractText
Hypoxia triggers the transcription of genes responsible for cell survival via the key player transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha). Overexpression of this protein has been implicated in cardiovascular disorders, carcinogenesis and cancer progression. For functional and diagnostic studies on the HIF-1alpha protein, we have identified single-domain antibody fragments directed against this protein by using a llama-derived nonimmune phage display library. This library displays the variable domains of the heavy-chain antibody subclass, found in these animals. Phage display selection with six recombinant HIF-1alpha proteins yielded five different antibody fragments. By epitope-mapping, we show that all five antibody fragments bind within the functionally important oxygen-dependent degradation domain of the HIF-1alpha protein. Two of these antibody fragments were engineered into bivalent antibodies that were able to detect human HIF-1alpha by immunohistochemistry, Western blotting and immunoprecipitation, and mouse HIF-1alpha by immunofluorescence and immunoprecipitation. These are the first single-domain antibody fragments that may be used in exploration of HIF-1alpha as a possible therapeutic target through molecular applications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-56
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16482104-Amino Acid Sequence, pubmed-meshheading:16482104-Animals, pubmed-meshheading:16482104-Antibody Affinity, pubmed-meshheading:16482104-Binding, Competitive, pubmed-meshheading:16482104-Camelids, New World, pubmed-meshheading:16482104-Cloning, Molecular, pubmed-meshheading:16482104-Humans, pubmed-meshheading:16482104-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:16482104-Immunoglobulin Fragments, pubmed-meshheading:16482104-Immunohistochemistry, pubmed-meshheading:16482104-Immunoprecipitation, pubmed-meshheading:16482104-Mice, pubmed-meshheading:16482104-Microscopy, Fluorescence, pubmed-meshheading:16482104-Molecular Sequence Data, pubmed-meshheading:16482104-Peptide Library, pubmed-meshheading:16482104-Protein Structure, Tertiary, pubmed-meshheading:16482104-Recombinant Proteins
pubmed:year
2006
pubmed:articleTitle
Identification by phage display of single-domain antibody fragments specific for the ODD domain in hypoxia-inducible factor 1alpha.
pubmed:affiliation
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't