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

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.