Abstract
Peptide agonists and antagonists of both bradykinin (BK) B(1) and B(2) receptors (B(1)R, B(2)R) are known to tolerate to a certain level N-terminal sequence extensions. Using this strategy, we produced and characterized the full set of fluorescent ligands by extending both agonists and antagonist peptides at both receptor subtypes with 5(6)-carboxyfluorescein (CF) and the ε-aminocaproyl (ε-ACA) optional spacer. Alternatively, kinin receptor ligands were extended with another carboxylic acid cargo (chlorambucil, biotinyl, pentafluorocinnamoyl, AlexaFluor-350 (AF350), ferrocenoyl, cetirizine) or with fluorescein isothiocyanate. N-terminal extension always reduced receptor affinity, more importantly for bulkier substituents and more so for the agonist version compared to the antagonist. This loss was generally alleviated by the presence of the spacer and modulated by the species of origin for the receptor. We report and review the pharmacological properties of these N-terminally extended peptides and the use of fluorophore-conjugated ligands in imaging of cell receptors and of angiotensin converting enzyme (ACE) in intact cells. Antagonists (B(1)R: B-10376: CF-ε-ACA-Lys-Lys-[Hyp(3), CpG(5), D-Tic(7), CpG(8)]des-Arg(9)-BK; B(2)R: B...Continue Reading
References
Aug 1, 1987·Immunology and Cell Biology·M J SmythI F McKenzie
Mar 1, 1995·Immunopharmacology·L LevesqueF Marceau
May 1, 1996·British Journal of Pharmacology·F GobeilD Regoli
Nov 8, 1996·The Journal of Biological Chemistry·K JarnaginR Freedman
Jun 17, 2000·Hypertension·S HouleF Marceau
Feb 21, 2002·Molecular Pharmacology·Thierry SabourinFrançois Marceau
Jul 17, 2004·Regulatory Peptides·Martin O'RourkeChris Shaw
Oct 2, 2004·Nature Reviews. Drug Discovery·François Marceau, Domenico Regoli
Mar 1, 2005·Pharmacological Reviews·L M Fredrik Leeb-LundbergBruce L Zuraw
May 28, 2005·The Journal of Pharmacology and Experimental Therapeutics·Jean-Philippe FortinFrançois Marceau
Aug 22, 2006·Current Topics in Medicinal Chemistry·Jean-Philippe Fortin, François Marceau
Jan 10, 2008·International Immunopharmacology·Lajos GeraFrançois Marceau
May 10, 2008·Bone·Anna Bernhold BrechterUlf H Lerner
Jun 21, 2008·Peptides·Marie-Thérèse BawolakFrançois Marceau
Jan 13, 2009·The Journal of Pharmacology and Experimental Therapeutics·Marie-Thérèse BawolakFrançois Marceau
Feb 3, 2009·Breast Cancer Research and Treatment·Luis MolinaMaria T Poblete
Jun 26, 2009·Expert Opinion on Therapeutic Patents·Christopher I FinchamDaniela Fattori
Sep 30, 2009·British Journal of Pharmacology·Marie-Thérèse BawolakFrançois Marceau
May 11, 2010·Peptides·Gérémy Abdull KoumbadingaFrançois Marceau
Jul 16, 2011·European Journal of Pharmacology·Marie-Thérèse BawolakFrançois Marceau
Nov 24, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Marie-Thérèse BawolakFrançois Marceau
Citations
Oct 26, 2012·Expert Opinion on Drug Discovery·Eric T WhalleyKanti D Bhoola
Oct 1, 2013·Pharmacology Research & Perspectives·Xavier Charest-MorinFrançois Marceau
Sep 11, 2013·International Immunopharmacology·Lajos GeraFrançois Marceau
Mar 5, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xavier Charest-MorinFrançois Marceau
Sep 24, 2013·Biochimica Et Biophysica Acta·Rajashri SridharanMark E Dumont
Mar 19, 2014·Frontiers in Pharmacology·Xavier Charest-MorinFrançois Marceau
Sep 28, 2016·BMC Research Notes·Lajos GeraFrançois Marceau
Nov 11, 2019·International Journal of Molecular Sciences·Dragoș-Valentin PredescuSilviu-Cristian Voinea
Aug 23, 2020·Pharmaceuticals·Joseph LauKuo-Shyan Lin
Dec 10, 2014·Cancer Research·Kuo-Shyan LinFrançois Bénard
Feb 28, 2020·International Immunopharmacology·François MarceauLajos Gera