Computational structure-activity study directs synthesis of novel antitumor enkephalin analogs

M. Gredičak, F. Supek, M. Kralj, Z. Majer, M. Hollósi, T. Šmuc, K. Mlinarić-Majerski, Š Horvat

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15 Citations (Scopus)

Abstract

The capability of a Support Vector Machines QSAR model to predict the antiproliferative ability of small peptides was evaluated by screening a virtual library of enkephalin-like analogs modified by incorporation of the (R,S)-(1-adamantyl)glycine (Aaa) residue. From an initial set of 390 compounds, the peptides, Tyr-Aaa-Gly-Phe-Met (2), Tyr-Aaa-Gly-Phe-Phe (3), Phe-Aaa-Gly-Phe-Phe (4) and Phe-Aaa-Gly-Phe-Met (5) were selected, synthesized and their antitumor activity was tested and compared to that of Met-enkephalin (1). The antiproliferative activity correlated with the computational prediction and with the foldamer-forming ability of the studied peptides. The most active compounds were the hydrophobic peptides, Phe-Aaa-Gly-Phe-Phe (4) and Phe-Aaa-Gly-Phe-Met (5), having a greater propensity to adopt folded structures than the other peptides.

Original languageEnglish
Pages (from-to)1185-1191
Number of pages7
JournalAmino Acids
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 1 2010

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Keywords

  • (1-Adamantyl)glycine
  • CD spectroscopy
  • Enkephalin analogs
  • In vitro antiproliferative activity
  • Peptide synthesis
  • QSAR study

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Gredičak, M., Supek, F., Kralj, M., Majer, Z., Hollósi, M., Šmuc, T., Mlinarić-Majerski, K., & Horvat, Š. (2010). Computational structure-activity study directs synthesis of novel antitumor enkephalin analogs. Amino Acids, 38(4), 1185-1191. https://doi.org/10.1007/s00726-009-0329-5