Linked Life Data

17118791

Source:http://linkedlifedata.com/resource/pubmed/id/17118791

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2006-11-22
pubmed:abstractText
p-Azido-phenylalanine has been frequently used for photoaffinity labeling of target proteins such as the angiotensin receptors. However, chemical studies showed that simple aryl nitrenes first react intramolecularly, forming a semistable cyclic keteneimine and then reacting with nucleophile residues in the target structure like those of lysine and arginine. We synthesized 3,5-difluoro-4-azidophenylalanine where the formation of the keteneimine is prevented and where photoincorporation should be due to nonselective nitrene insertion only. This new amino acid was introduced in position 8 of angiotensin II and compared with the corresponding azidophenylalanine peptide using human AT1 receptor as target. The new photolabel maintained full agonist activity and a similar yield of photolabeling but without the previously observed gradual hydrolysis. Several selective proteolyses of the labeled receptor indicate that the new photolabel forms three simultaneous contact regions on the hAT1 receptor, suggestive of a nonselective behavior of the photolabel. A major contact was established in the sixth transmembrane domain but also in the third and seventh domain. Our results are in excellent agreement with those recently obtained from methionine proximity assay studies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1079-9893
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
435-51
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Synthesis of an agonistic, difluoro-azido photolabel of angiotensin II and labeling of the AT1 receptor: transmembrane domains 3, 6, and 7 form the ligand-binding pocket.
pubmed:affiliation
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't