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

Autori
Gredičak, Matija ; Supek, Fran ; Kralj, Marijeta, Majer, Zsuzsa ; Hollosi, Miklos ; Šmuc, Tomislav ; Mlinarić-Majerski, Kata ; Horvat, Štefica

Izvornik
Amino acids (Wien) (0939-4451) 38 (2010), 4; 1185-1191

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Enkephalin analogs ; (1-adamantyl)glycine ; QSAR study ; CD spectroscopy ; In vitro antiproliferative activity ; Peptide synthesis

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Informacijske i komunikacijske znanosti

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