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.
Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth / Saxena, P; Severi, L; Santucci, M; Taddia, ; Ferrari, S; Luciani, R; Marverti, G; Marraccini, C; Tondi, D; Mor, M; Scalvini, L; Vitiello, S; Losi, L; Fonda, S; Pacifico, S; Guerrini, R; D'Arca, D; Ponterini, G; Costi, Mp. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 61:16(2018), pp. 7374-7380. [10.1021/acs.jmedchem.7b01699]
Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth
Mor M;Scalvini L;
2018-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
