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Differential structural requirements for the MSH and MCH activities of melanin concentrating hormone
Authors:M E Hadley  C Zechel  B C Wilkes  A M Castrucci  M A Visconti  M Pozo-Alonso  V J Hruby
Affiliation:1. Department of Anatomy University of Arizona, Tucson, Arizona 85721 U.S.A.;2. Department of Chemistry University of Arizona, Tucson, Arizona 85721 U.S.A.;3. Departmento de Fisiologia, Universidade de São Paulo CP11176, São Paulo, Brazil;1. Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, Ningbo 315201, PR China;2. Department of NanoEngineering, University of California San Diego (UCSD), La Jolla, CA 92093, USA;3. School of Advanced Materials, Peking University, Shenzhen Graduate School, Shenzhen 518055, PR China;4. Neutron Scattering Division, Oak Ridge National Laboratory (ORNL), 1 Bethel Valley Road, Oak Ridge, TN 37831-6473, USA;5. Shanghai Synchrotron Radiation Facility, Chinese Academy of Sciences, Zhangjiang High-Tech. Park, Pudong New Area, Shanghai 201204, PR China;6. Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing 100049, PR China;7. Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, PR China;8. Spallation Neutron Source Science Center, Dongguan 523803, PR China;9. Songshan Lake Materials Laboratory, Dongguan 523808, PR China;10. School of Chemical Engineering and Technology, China University of Mining and Technology (CUMT), Xuzhou 221116, P. R. China;11. University of Nottingham Ningbo China (UNNC), Taikang East Road 199, Ningbo 315100, P. R. China;1. Institute of Nutrition, College of Healthcare, China Medical University, Taichung 40402, Taiwan;2. Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan;3. Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan;4. Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan;5. Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan
Abstract:H-Asp-Thr-Met-Arg-Cys-Met-Val-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Glu-Val-OH , melanin concentrating hormone (MCH), exhibits both melanin granule concentrating and dispersing (MSH-like) activities. Fragment analogues of MCH were synthesized as described herein and the melanotropic activities of the peptides were determined. In the frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays, the 5-17 and 5-14 fragments of MCH were inactive (at concentrations of 10(-5)M or less), whereas the 1-14 sequence exhibited minimal (about 10%) MSH-like activity compared to MCH, which, as reported previously, was about 600 times less active than alpha-MSH. In the teleost (fish) skin bioassay, the MCH5-17 analogue was equipotent to MCH, whereas the 1-14 analogue was 10-30 times and the cyclic N- and C- terminal truncated analogue, MCH5-14, was about 300 times less active than MCH. These results suggest that the N-terminal sequence is particularly critical to MSH-like activity in the tetrapod species studied, whereas other structural regions of MCH, particularly in the C-terminal, are more related to MCH activity in teleosts.
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