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Labeling the granulocyte C5a receptor with a unique photoreactive probe

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:6380953

Human C5a anaphylatoxin is a complement-derived chemotactic factor that binds to specific receptors that are found in the granulocyte plasma membrane. These receptors, or a specific subunit of these receptors, can be covalently labeled with a unique photoreactive analog of human C5a. This photoaffinity probe, p-azidobenzoyl-2-mercapto-N-ethylamide-C5a (ABMEA-SC5a), was synthesized by coupling p-azidobenzoyl-2-mercapto-N-ethylamide-2'-thiopyridine disulfide to human C5a after it had been partially reduced with dithiothreitol. Both direct and competitive binding studies demonstrated that a radioiodinated ABMEA-SC5a derivative retained the capacity to specifically bind to either neutrophil or U937 cell C5a receptors. Half-maximal binding of the photoreactive analog was observed at a concentration of 1 to 2 nM, a value that is comparable to that observed when /sup 125/I-C5a is employed as the ligand. The covalent adducts that were formed after irradiation of /sup 125/I-ABMEA-SC5a that had been prebound to either neutrophil or U937 cell plasma membranes were found to have an apparent molecular mass of 52,000 daltons when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis techniques. These findings demonstrate that the C5a receptors found on human neutrophils and other granulocytes are not only functionally similar, but biochemically similar as well.

OSTI ID:
6380953
Journal Information:
J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 12; ISSN JBCHA
Country of Publication:
United States
Language:
English