Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth
journal contributionposted 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.
Read the peer-reviewed publication
Molecular dynamics calculationsintracellular protein modulationthymidylate synthaseProline Mutated LR Peptides Inhibiting Human Thymidylate SynthaseConformational Propensityproline-mutated LR peptidesOvarian Cancer Cell Growth LRcancer cell growthdichroism spectraBiological Studiescell growth inhibition