Design and synthesis of peptidic partial agonists of human neuromedin U receptor 1 with enhanced serum stability |
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| Affiliation: | 1. Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan;2. Department of Environmental Biochemistry, Kyoto Pharmaceutical University, 5 Misasaginakauchi-cho, Yamashina, Kyoto 607-8414, Japan;3. Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan;4. Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India;2. Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India;3. Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India;4. School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;1. Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Republic of Korea;2. Department of Food Science and Biotechnology, Daegu University, Gyeongsan 38453, Republic of Korea;3. Cell and Matrix Research Institute (CMRI), Kyungpook National University, Daegu 41940, Republic of Korea;4. Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, Republic of Korea;5. Department of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, Republic of Korea;6. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea;7. Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, Republic of Korea;8. Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea;1. Laboratoire de Biotechnologies Végétales et Ethnobotanique, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia, Algeria;2. CIBER-EHD, Department of Pharmacology, Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain;3. Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain;4. Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, 18012 Granada, Spain;1. Discipline of Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, India;2. Discipline of Chemistry, Indian Institute of Technology Gandhinagar, Gujarat, India |
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| Abstract: | Neuromedin U (NMU) activates two receptors (NMUR1 and NMUR2) and is a promising candidate for development of drugs to combat obesity. Previously, we obtained hexapeptides as selective full NMUR agonists. Development of a partial agonist which mildly activates receptors is an effective strategy which lead to an understanding of the functions of NMU receptors. In 2014, we reported hexapeptide 3 (CPN-124) as an NMUR1-selective partial agonist but its selectivity and serum stability were unsatisfactory. Herein, we report the development of a hexapeptide-type partial agonist (8, CPN-223) based on a peptide (3) but with higher NMUR1-selectivity and enhanced serum stability. A structure-activity relationship study of synthetic pentapeptide derivatives suggested that a hexapeptide is a minimum structure consistent with both good NMUR1-selective agonistic activity and serum stability. |
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| Keywords: | Neuromedin U receptor 1 Partial agonist Peptide Serum stability Thrombin |
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