Design, Synthesis, and Actions of an Innovative Bispecific Designer Peptide

Hypertension
Laura M G MeemsJohn C Burnett

Abstract

Despite optimal current therapies, cardiovascular disease remains the leading cause for death worldwide. Importantly, advances in peptide engineering have accelerated the development of innovative therapeutics for diverse human disease states. Additionally, the advancement of bispecific therapeutics targeting >1 signaling pathway represents a highly innovative strategy for the treatment of cardiovascular disease. We, therefore, engineered a novel, designer peptide, which simultaneously targets the pGC-A (particulate guanylyl cyclase A) receptor and the MasR (Mas receptor), potentially representing an attractive cardiorenoprotective therapeutic for cardiovascular disease. We engineered a novel, bispecific receptor activator, NPA7, that represents the fusion of a 22-amino acid sequence of BNP (B-type natriuretic peptide; an endogenous ligand of pGC-A) with Ang 1-7 (angiotensin 1-7)-the 7-amino acid endogenous activator of MasR. We assessed NPA7's dual receptor activating actions in vitro (second messenger production and receptor interaction). Further, we performed an intravenous peptide infusion comparison study in normal canines to study its biological actions in vivo, including in the presence of an MasR antagonist. Our in vivo...Continue Reading

References

Nov 1, 1991·Hypertension·C M FerrarioE A Tallant
Jan 30, 2002·The Journal of Biological Chemistry·Chad VickersPeter Tummino
Dec 14, 2002·Circulation Research·Toshihiro TsurudaJohn C Burnett
Jun 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Robson A S SantosThomas Walther
Jun 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yong LiH Eric Xu
Aug 2, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Carlos M FerrarioJewell A Jessup
Jul 7, 2007·Cardiovascular Drug Reviews·Aaron J Trask, Carlos M Ferrario
Nov 21, 2007·Molecular Medicine·Rodrigo Araújo Fraga-SilvaRobson Augusto Souza Santos
Apr 18, 2008·European Journal of Pharmacology·Dilek IusufAnton J M Roks
Apr 24, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Guido BoerrigterJohn C Burnett
Nov 12, 2010·The Journal of Biological Chemistry·X Edward ZhouH Eric Xu
Jul 30, 2011·Journal of the American College of Cardiology·Valentina CannoneJohn C Burnett
Dec 16, 2011·The Journal of Biological Chemistry·Xiaoyong ZhiH Eric Xu
Feb 7, 2012·The Journal of Clinical Investigation·Marica BordicchiaSheila Collins
Oct 13, 2012·Journal of the American College of Cardiology·Fima MacheretAlessandro Cataliotti
Oct 25, 2012·The Journal of Endocrinology·Robson A S SantosMichael Bader
Nov 6, 2012·Journal of the American College of Cardiology·Horng H ChenJohn C Burnett
Mar 26, 2013·Cardiovascular Research·Eliezer Joseph TassoneFrancesco Perticone
Mar 26, 2014·Hypertension·Robson Augusto Santos
Apr 30, 2014·Nature Reviews. Cardiology·Fan JiangCheng Zhang
Jul 16, 2014·Current Opinion in Nephrology and Hypertension·Daan J L van TwistPeter W de Leeuw
Dec 18, 2015·Circulation·UNKNOWN Writing Group MembersUNKNOWN Stroke Statistics Subcommittee
Jan 26, 2016·European Journal of Heart Failure·Paul M McKieHorng H Chen
Mar 10, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Anna M PapinskaKathleen E Rodgers
Apr 1, 2016·Physiological Reviews·Michaela Kuhn
Jun 15, 2016·Journal of the American Society of Nephrology : JASN·Fadia A KamalBurns C Blaxall

❮ Previous
Next ❯

Citations

Aug 21, 2019·Nature Reviews. Cardiology·Maria Paz OcaranzaSergio Lavandero
May 14, 2020·Hypertension·UNKNOWN Editors
Apr 7, 2020·British Journal of Pharmacology·Feby SaviraBing H Wang
Sep 10, 2020·International Journal of Molecular Sciences·Jairo Lumpuy-CastilloÓscar Lorenzo
Apr 4, 2021·Journal of Clinical Medicine·Samuel N HeymanZaid Abassi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.