N-terminal extended conjugates of the agonists and antagonists of both bradykinin receptor subtypes: structure-activity relationship, cell imaging using ligands conjugated with fluorophores and prospect for functionally active cargoes

Peptides
Lajos GeraF Marceau

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
Feb 21, 2002·Molecular Pharmacology·Thierry SabourinFrançois Marceau
Oct 2, 2004·Nature Reviews. Drug Discovery·François Marceau, Domenico Regoli
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
Jun 26, 2009·Expert Opinion on Therapeutic Patents·Christopher I FinchamDaniela Fattori
Sep 30, 2009·British Journal of Pharmacology·Marie-Thérèse BawolakFrançois 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

❮ Previous
Next ❯

Citations

Oct 26, 2012·Expert Opinion on Drug Discovery·Eric T WhalleyKanti D Bhoola
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
Feb 28, 2020·International Immunopharmacology·François MarceauLajos Gera

❮ Previous
Next ❯

Related Concepts

Related Feeds

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.