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

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

Research output: Contribution to journalArticle

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 2010

Fingerprint

Enkephalins
Glycine
Peptides
Digital Libraries
Methionine Enkephalin
Quantitative Structure-Activity Relationship
Support vector machines
Screening

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

Computational structure-activity study directs synthesis of novel antitumor enkephalin analogs. / Gredičak, M.; Supek, F.; Kralj, M.; Majer, Zs.; Hollósi, M.; Šmuc, T.; Mlinarić-Majerski, K.; Horvat, Š.

In: Amino Acids, Vol. 38, No. 4, 04.2010, p. 1185-1191.

Research output: Contribution to journalArticle

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, vol. 38, no. 4, pp. 1185-1191. https://doi.org/10.1007/s00726-009-0329-5
Gredičak, M. ; Supek, F. ; Kralj, M. ; Majer, Zs. ; Hollósi, M. ; Šmuc, T. ; Mlinarić-Majerski, K. ; Horvat, Š. / Computational structure-activity study directs synthesis of novel antitumor enkephalin analogs. In: Amino Acids. 2010 ; Vol. 38, No. 4. pp. 1185-1191.
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