Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth
| Autor: | Matteo Santucci, Simone Vitiello, Marco Mor, Donatella Tondi, Puneet Saxena, Laura Taddia, Gaetano Marverti, Chiara Marraccini, Leda Severi, Sergio Fonda, Remo Guerrini, Stefania Ferrari, Laura Scalvini, Maria Paola Costi, Glauco Ponterini, Domenico D'Arca, Rosaria Luciani, Lorena Losi, Salvatore Pacifico |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Circular dichroism Proline Protein Conformation Antineoplastic Agents Molecular Dynamics Simulation medicine.disease_cause Thymidylate synthase NO 03 medical and health sciences 0302 clinical medicine Protein structure Cell Line Tumor Drug Discovery medicine Humans Enzyme Inhibitors Ovarian Neoplasms Mutation biology Cell growth Chemistry Circular Dichroism Thymidylate Synthase 030104 developmental biology Biochemistry Cell culture 030220 oncology & carcinogenesis Cancer cell biology.protein Molecular Medicine Female Peptides |
| Zdroj: | Journal of Medicinal Chemistry. 61:7374-7380 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.7b01699 |
| Popis: | LR and [d-Gln4]LR peptides bind the monomer-monomer interface of human thymidylate synthase and inhibit cancer cell growth. Here, proline-mutated LR peptides were synthesized. Molecular dynamics calculations and circular dichroism spectra have provided a consistent picture of the conformational propensities of the [Pro n]-peptides. [Pro3]LR and [Pro4]LR show improved cell growth inhibition and similar intracellular protein modulation compared with LR. These represent a step forward to the identification of more rigid and metabolically stable peptides. |
| Databáze: | OpenAIRE |
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