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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adamantane / analogs & derivatives
-
Adamantane / chemistry
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Artificial Intelligence
-
Cell Line, Tumor
-
Circular Dichroism
-
Computational Biology / methods*
-
Cytostatic Agents / chemical synthesis*
-
Cytostatic Agents / chemistry
-
Cytostatic Agents / pharmacology
-
Databases, Factual
-
Drug Design*
-
Enkephalin, Methionine / analogs & derivatives*
-
Enkephalin, Methionine / chemistry
-
Enkephalin, Methionine / pharmacology
-
Humans
-
Hydrophobic and Hydrophilic Interactions
-
Models, Molecular*
-
Oligopeptides / chemical synthesis
-
Oligopeptides / chemistry
-
Oligopeptides / pharmacology
-
Principal Component Analysis
-
Protein Conformation
-
Quantitative Structure-Activity Relationship
-
Software
Substances
-
Antineoplastic Agents
-
Cytostatic Agents
-
Oligopeptides
-
phenylalanyl-1-adamantylacetic acid-glycyl-phenylalanyl-methionine
-
phenylalanyl-1-adamantylacetic acid-glycyl-phenylalanyl-phenylalanine
-
Enkephalin, Methionine
-
Adamantane