Identification and in Vivo and in Vitro Characterization of Long Acting and Melanocortin 4 Receptor (MC4-R) Selective α-Melanocyte-Stimulating Hormone (α-MSH) Analogues
| العنوان: | Identification and in Vivo and in Vitro Characterization of Long Acting and Melanocortin 4 Receptor (MC4-R) Selective α-Melanocyte-Stimulating Hormone (α-MSH) Analogues |
|---|---|
| المؤلفون: | Henning Thøgersen, Leif Christensen, Helle Birk Olsen, Cecilia Nilsson, Ulrich Sensfuss, Thomas Kruse Hansen, Kilian Conde-Frieboes, Kirsten Raun, Kirsten Dahl, Birgit Sehested Hansen, Jane Spetzler, Birgitte Schjellerup Wulff, Jesper Lau |
| المصدر: | Journal of Medicinal Chemistry. 55:1969-1977 |
| بيانات النشر: | American Chemical Society (ACS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Melanocyte-stimulating hormone, Stereochemistry, Injections, Subcutaneous, Rats, Sprague-Dawley, Eating, Structure-Activity Relationship, In vivo, Drug Discovery, Animals, Receptor, chemistry.chemical_classification, Fatty Acids, Fatty acid, Rats, Amino acid, Melanocortin 4 receptor, Solubility, chemistry, Biochemistry, alpha-MSH, Receptor, Melanocortin, Type 4, Molecular Medicine, Anti-Obesity Agents, Long chain fatty acid, Melanocortin |
| الوصف: | We report in vitro and in vivo data of new α-melanocyte-stimulating hormone (α-MSH) analogues which are N-terminal modified with a long chain fatty acid derivative. While keeping the pharmacophoric motif (d-Phe-Arg-Trp) fixed, we tried to improve selectivity and physicochemical parameters like solubility and stability of these analogues by replacing amino acids further away from the motif. Receptor specific changes in binding affinity to the melanocortin receptors were observed between the acetyl derivatives and the fatty acid analogues. Furthermore, amino acids at the N-terminal of α-MSH (Ser-Tyr-Ser) not considered to be part of the pharmacophore were found to have an influence on the MC4/MC1 receptor selectivity. While the acetyl analogues have an in vivo effect for around 7 h, the long chain fatty acid analogues have an effect up to 48 h in an acute feeding study in male Sprague-Dawley rats after a single subcutaneous administration. |
| تدمد: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm201489a |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::506c57b49d0e739285b222ba20d7d798 https://doi.org/10.1021/jm201489a |
| رقم الانضمام: | edsair.doi.dedup.....506c57b49d0e739285b222ba20d7d798 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
|---|---|
| DOI: | 10.1021/jm201489a |