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

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.
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]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2852364
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact