Total synthesis of human plasma apolipoprotein C-II |
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| Institution: | 1. Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 USA;2. Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 USA;3. Department of Pharmacology and Biophysics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 USA;4. Merrell Dow Research Institute, 2110 East Galbraith Road, Cincinnati, Ohio 45215 USA;1. Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece;2. Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey;3. The Hatter Cardiovascular Institute, University College London, London, United Kingdom;4. Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria;5. Division of Cardiology, Department of Medicine, Department of Physiology, and Molecular Biology Institute, UCLA, Los Angeles, CA, USA;7. Department of Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic;8. Genomics Medicine Unit, Navarra Institute for Health Research – IdiSNA, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Pamplona, Spain;9. Centre for Academic Primary Care, School of Medicine, University of Nottingham, United Kingdom;10. Department of Medicine and Surgery, University of Perugia, Italy;11. Internal Medicine Department, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania;12. Department of Endocrinology, Tan Tock Seng Hospital, Singapore;13. Cardiology Department, Institute of Endocrinology and Metabolism, Kyiv, Ukraine;14. Unidade I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal;15. Universidade de Lisboa, Faculdade de Ciências, BioISI – Biosystems & Integrative Sciences Institute, Lisboa, Portugal;p. Division of Vascular and Endovascular Surgery, Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy;q. Sumy State University, Sumy, Ukraine;r. Tallinn University of Technology, Tallinn, Estonia;s. Cardiology Clinic, Ankara Bilkent City Hospital, Ankara, Turkey;t. Nantes Université, CNRS, INSERM, l''institut du Thorax, Nantes, France;u. Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università Degli Studi di Milano, Milan, Italy;v. Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom;w. Barts Interventional Group, Barts Heart Centre, St. Bartholomew''s Hospital, London, United Kingdom;x. Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium;y. Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, Moscow, Russia;z. \"Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania;11. Institute of Cardiovascular Diseases Timisoara, Timisoara, Romania;12. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy;13. Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium;14. Department of Prevention and Treatment of Emergency Conditions, L.T. Malaya Therapy National Institute NAMSU, Kharkiv, Ukraine;15. Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation, Tashkent, Uzbekistan;16. Department of Medicine, University of Padova, Italy;17. Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074, Aachen, Germany;18. Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), RWTH Aachen University, 52074, Aachen, Germany;19. Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, 80336, Munich, Germany;110. Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074, Aachen, Germany;111. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria;1. Division of Cardiology, Department of Medicine, UCLA, Los Angeles, CA, USA;2. Department of Physiology, UCLA, Los Angeles, CA, USA;3. Molecular Biology Institute, UCLA, Los Angeles, CA, USA;1. Department of Exercise Science, University of South Carolina, Columbia, SC, USA;2. CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA;3. Quest Diagnostics Cardiometabolic Center of Excellence at Cleveland HeartLab, Cleveland, OH, USA;4. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA;5. Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA;6. Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA;7. Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA |
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| Abstract: | Apolipoprotein C-II (apoC-II), a protein of 79 amino acid residues present in very low density lipoproteins, enhances the lipoprotein lipase (LpL)-catalyzed hydrolysis of triacylglycerols transported in plasma triglyceride-rich lipoproteins. To elucidate the structure-activity relationship of this activator protein, the complete amino acid sequence of apoC-II has been synthesized by the solid-phase method with Boc-amino acid derivatives and phenylacetamidomethyl resin. The crude peptide was purified to homogeneity in 10% yield by a combination of ion-exchange and preparative high-performance liquid chromatography (HPLC). The purified peptide had the expected amino-terminal sequence and amino acid composition. Synthetic and native apoC-II were indistinguishable by cochromatography on analytical HPLC, peptide mapping of tryptic digest, radioimmunoassay, and activation of LpL with both artificial and lipoprotein substrates. |
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