Synthesis of cyclic α-MSH peptides |
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Authors: | Wim MM Schaaper Roger AH Adan Truus A Posthuma Julia Oosterom Willem-Hendrik Gispen Rob H Meloen |
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Institution: | (1) Institute for Animal Science and Health, ID-DLO, Edelherweg 15, P.O. Box 65, 8200 AB Lelystad, The Netherlands;(2) Rudolf Magnus Institute for Neurosciences, University of Utrecht, P.O. Box 80040, 3508 TA Utrecht, The Netherlands |
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Abstract: | Summary Cyclic lactam analogs of α-melanocyte stimulating hormone (α-MSH) have been shown to be potent agonists in the frog skin bioassay
Al-Obeidi, F. et al., J. Med. Chem., 32 (1989) 2555], demonstrating melanocortin-1 (MC1) receptor activity. We synthesized
cyclic α-MSH(1–13) and α-MSH(4–10) lactam analogs. The peptides were synthesized using Fmoc chemistry. We improved the cyclization
procedure: side chains of Asp5 and Lys10 from the deprotected peptide were coupled in DMF to form a cyclic lactam, using an excess of PyBOP reagent and DIEA as a
base. The cyclization reaction was completed within 1 h and was almost quantitative. We also synthesized an α-MSH analog cyclized
via a disulphide bridge. The peptides were tested for their selectivity for the rat MC4 receptor. Cyclization and substitutions
at position 7 dramatically influenced the selectivity for the rMC4 receptor. |
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Keywords: | cyclization lactam melanocortin receptor PyBOP |
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