Bifunctional epitope-agonist ligands of the bradykinin B(2) receptor.

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 [H-3]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.