Abstract
The human adrenomedullin (ADM) is a 52 amino acid peptide hormone belonging to the calcitonin family of peptides, which plays a major role in the development and regulation of cardiovascular and lymphatic systems. For potential use in clinical applications, we aimed to investigate the fate of the peptide ligand after binding and activation of the adrenomedullin receptor (AM1), a heterodimer consisting of the calcitonin receptor-like receptor (CLR), a G protein-coupled receptor, associated with the receptor activity-modifying protein 2 (RAMP2). Full length and N-terminally shortened ADM peptides were synthesized using Fmoc/tBu solid phase peptide synthesis and site-specifically labeled with the fluorophore carboxytetramethylrhodamine (Tam) either by amide bond formation or copper(I)-catalyzed azide alkyne cycloaddition. For the first time, Tam-labeled ligands allowed the observation of co-internalization of the whole ligand-receptor complex in living cells co-transfected with fluorescent fusion proteins of CLR and RAMP2. Application of a fluorescent probe to track lysosomal compartments revealed that ADM together with the CLR/RAMP2-complex is routed to the degradative pathway. Moreover, we found that the N-terminus of ADM is not...Continue Reading
References
Jan 1, 1997·Critical Reviews in Neurobiology·S J Wimalawansa
Jun 10, 1998·Nature·L M McLatchieS M Foord
Jul 7, 2000·The Journal of Biological Chemistry·K KuwasakoT Sakata
Apr 2, 2003·Regulatory Peptides·Debbie L HayDavid M Smith
Oct 28, 2005·British Journal of Cancer·L L NikitenkoR Bicknell
Feb 24, 2006·Journal of Cell Science·Leonid L NikitenkoMargaret C P Rees
Apr 21, 2007·Nature Protocols·Karin L Heckman, Larry R Pease
Jul 5, 2008·Cellular Signalling·Ilka BöhmeAnnette G Beck-Sickinger
Sep 21, 2010·The Journal of Organic Chemistry·Changwei ShaoYuefei Hu
Jul 29, 2011·The Journal of Organic Chemistry·Changwei ShaoYuefei Hu
Jan 6, 2012·Recent Patents on Endocrine, Metabolic & Immune Drug Discovery·Bernard M Y Cheung, Fai Tang
May 15, 2012·Current Hypertension Reviews·Natalie O KarpinichKathleen M Caron
Mar 2, 2013·Biological Chemistry·Stefanie BabilonAnnette G Beck-Sickinger
May 31, 2014·Peptides·Keishi KuboKazuo Kitamura
Jul 30, 2014·Angewandte Chemie·Veronika MädeAnnette G Beck-Sickinger
May 20, 2015·Molecular Cell·Jason M BooeAugen A Pioszak
Citations
May 12, 2016·Journal of Medicinal Chemistry·Ria SchönauerAnnette G Beck-Sickinger
Jan 13, 2018·Shock·Christopher GevenPeter Pickkers
Jul 7, 2018·ChemMedChem·Jan-Patrick FischerAnnette G Beck-Sickinger
Feb 6, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Ria SchönauerAnnette G Beck-Sickinger
Mar 10, 2018·Frontiers in Immunology·Christopher GevenPeter Pickkers
Jan 27, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Jan-Patrick FischerAnnette G Beck-Sickinger
Dec 29, 2018·European Journal of Heart Failure·Adriaan A VoorsJaved Butler
Jan 1, 2021·Journal of Internal Medicine·D van LierP Pickkers
May 9, 2021·Journal of Biochemistry·Nobuko KuroishiKazuo Kitamura
Jul 23, 2019·Biochemistry·Hala MusaDebbie L Hay
Apr 17, 2020·ACS Pharmacology & Translational Science·Michael L GareljaDebbie L Hay