title: Bifunctional epitope-agonist ligands of the bradykinin B(2) receptor.
abstract: Two bradykinin (BK) B(2) receptor agonists N-terminally extended with the myc epitope were synthesized and evaluated: myc-KPG-BK and myc-KGP-B-9972. The latter was modeled on the inactivation-resistant agonist B-9972 (D-Arg(0), Hyp(3), Igl(5), Oic(7), Igl(8)-BK) and is also resistant to endosomal inactivation. Despite a large loss of affinity relative to the parent peptide, the tagged analogs are conventional agonists in the umbilical vein contractility assay and compete for [(3)H]BK binding at the rabbit B(2) receptor. Endocytosed myc-KGP-B-9972 most effectively carried AlexaFluor-488-conjugated anti-myc monoclonal antibodies into intact cells expressing the B(2) receptor. Results support the prospects of functionally-active cargoes entering cells in a pharmacologically controlled manner.
authors.affiliation: Department of Biochemistry, University of Colorado Denver, Aurora CO 80045, USA.
authors.forename: Lajos
authors.initials: L
authors.lastname: Gera
authors.forename: Caroline
authors.initials: C
authors.lastname: Roy
authors.forename: François
authors.initials: F
authors.lastname: Marceau
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D004705:Endocytosis; D000939:Epitopes / Q000378:metabolism*; D016259:Genes, myc; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D043782:Receptor, Bradykinin B2 / Q000819:agonists*
chemical_list: D000939:Epitopes; D008024:Ligands; D043782:Receptor, Bradykinin B2