2. Academic Validation
  3. Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth

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

  • J Med Chem. 2018 Aug 23;61(16):7374-7380. doi: 10.1021/acs.jmedchem.7b01699.
Puneet Saxena 1,  Leda Severi 1,  Matteo Santucci 1,  Laura Taddia 1,  Stefania Ferrari 1,  Rosaria Luciani 1,  Gaetano Marverti 2,  Chiara Marraccini 1,  Donatella Tondi 1,  Marco Mor 3,  Laura Scalvini 3,  Simone Vitiello 1,  Lorena Losi 1 4,  Sergio Fonda 1,  Salvatore Pacifico 5,  Remo Guerrini 5 6,  Domenico D'Arca 2,  Glauco Ponterini 1,  Maria Paola Costi 1
Affiliations

Affiliations

  • 1 Department of Life Sciences , University of Modena and Reggio Emilia , Via Campi 103 , 41125 Modena , Italy.
  • 2 Department of Biomedical Sciences, Metabolic and Neural Sciences , University of Modena and Reggio Emilia , Via Campi 287 , 41125 Modena , Italy.
  • 3 Dipartimento di Scienze degli Alimenti e del Farmaco , Università di Parma , Parco Area delle Scienze 27/A , I-43124 Parma , Italy.
  • 4 Pathological Anatomy , Via del Pozzo 71 , 41124 Modena , Italy.
  • 5 Department of Chemical and Pharmaceutical Sciences , University of Ferrara , Via Luigi Borsari 46 , 44121 Ferrara , Italy.
  • 6 LTTA (Laboratorio per le Tecnologie delle Terapie Avanzate) , Via Fossato di Mortara 17-19 , 44100 Ferrara , Italy.
PMID: 30035541 DOI: 10.1021/acs.jmedchem.7b01699
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.

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