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Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth

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posted on 23.07.2018, 00:00 authored by Puneet Saxena, Leda Severi, Matteo Santucci, Laura Taddia, Stefania Ferrari, Rosaria Luciani, Gaetano Marverti, Chiara Marraccini, Donatella Tondi, Marco Mor, Laura Scalvini, Simone Vitiello, Lorena Losi, Sergio Fonda, Salvatore Pacifico, Remo Guerrini, Domenico D’Arca, Glauco Ponterini, Maria Paola Costi
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 [Pron]-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.

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