Design, synthesis, and biological studies of efficient multivalent melanotropin ligands: tools toward melanoma diagnosis and treatment
| Autor: | Ronald M. Lynch, Liping Xu, Nabila Brabez, Robert J. Gillies, Gérard Chassaing, Solange Lavielle, Victor J. Hruby |
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| Přispěvatelé: | Université Pierre et Marie Curie - Paris 6 (UPMC) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Dendrimers
endocrine system Skin Neoplasms Ligands Binding Competitive 01 natural sciences Article Structure-Activity Relationship 03 medical and health sciences Transduction (genetics) chemistry.chemical_compound Dendrimer Drug Discovery Cyclic AMP Humans Structure–activity relationship Cyclic adenosine monophosphate Melanocyte-Stimulating Hormones Receptor Melanoma 030304 developmental biology 0303 health sciences 010405 organic chemistry Ligand Chemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry HEK 293 cells Combinatorial chemistry 0104 chemical sciences HEK293 Cells Biochemistry Drug Design Receptor Melanocortin Type 4 Molecular Medicine Melanocortin Peptides |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2011, 54 ((20)), pp.7375-84. ⟨10.1021/jm2009937⟩ Journal of Medicinal Chemistry, 2011, 54 ((20)), pp.7375-84. ⟨10.1021/jm2009937⟩ |
| ISSN: | 0022-2623 1520-4804 |
| DOI: | 10.1021/jm2009937⟩ |
| Popis: | International audience; To achieve early detection and specific cancer treatment, we propose the use of multivalent interactions in which a series of binding events leads to increased affinity and consequently to selectivity. Using melanotropin (MSH) ligands, our aim is to target melanoma cells which overexpress melanocortin receptors. In this study, we report the design and efficient synthesis of new trivalent ligands bearing MSH ligands. Evaluation of these multimers on a cell model engineered to overexpress melanocortin 4 receptors (MC4R) showed up to a 350-fold increase in binding compared to the monomer, resulting in a trivalent construct with nanomolar affinity starting from a micromolar affinity ligand. Cyclic adenosine monophosphate (cAMP) production was also investigated, leading to more insights into the effects of multivalent compounds on transduction mechanisms. |
| Databáze: | OpenAIRE |
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