1033442-67-9Relevant academic research and scientific papers
Synthesis and evaluation of novel pyridine based PLG tripeptidomimetics
Saitton, Stina,Del Tredici, Andria L.,Saxin, Maria,Stenstroem, Tobias,Kihlberg, Jan,Luthman, Kristina
experimental part, p. 1647 - 1654 (2008/10/09)
Analogues of the pyridine based PLG (Pro-Leu-Gly-NH2) peptidomimetic 1 were synthesized and evaluated as dopamine modulating agents. Modifications in the position corresponding to the leucine side chain in PLG afforded derivatives 2, 3 and 4, substituted with H, Me and Bn instead of the isobutyl group, respectively. Changes in the proline residue produced derivative 5, substituted with a symmetrical piperidine ring instead of the pyrrolidine ring and 6, in which the pyrrolidine ring is connected to the pyridine ring via a hydroxymethyl group instead of a keto function. The peptidomimetics were tested for their ability to enhance the maximal effect of N-propylapomorphine (NPA) at dopamine D2 receptors in the functional cell-based R-SAT assay. Compounds 2, 3, and 4, produced a statistically significant increase in the maximal NPA response at 10 nM (117 ± 6%, 118 ± 6%, and 116 ± 3%, respectively), which is similar to the effect of PLG in this assay, whereas 5 was able to potentiate the response to a similar extent at 1 nM concentration (115 ± 5%). All derivatives produced a bell-shaped dose-response curve and none of the compounds were active at the D2 receptor alone, which indicates that the mechanism behind the activity of both the pyridine based mimetics 1-6 and PLG is the same. Interestingly, l-Pro-d-Leu-Gly-NH2 was found to be more potent than PLG and produced a 119 ± 1% increase in the NPA response at 1 nM. The Royal Society of Chemistry 2008.
