کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1355742 | 981059 | 2010 | 5 صفحه PDF | دانلود رایگان |
Peptidomimetic analogs of the peptide RRASVA, known as the “minimal substrate” of the catalytic subunit of the cAMP-dependent protein kinase (PKA), were synthesized by consecutive replacement of natural amino acids by their aza-β3 analogs. The peptidomimetics were tested as PKA substrates and the kinetic parameters of the phosphorylation reaction were determined. It was found that the interaction of these peptidomimetics with the enzyme active center was sensitive to the location of the backbone modification, while the maximal rate of the reaction was practically not affected by the structure of substrates. The pattern of molecular recognition of peptidomimetics was in agreement with the results of structure modeling and also with the results of computational docking study of peptide and peptidomimetic substrates with the active center of PKA. It was concluded that the specificity determining factors which govern substrate recognition by the enzyme should be grouped along the phosphorylatable substrate, and such clustering might open new perspectives for pharmacophore design of peptides and peptide-like ligands.
Peptidomimetics, synthesized by replacement of natural amino acids (left) by their aza-β3 analogs (right) in peptide RRASVA were phosphorylated by cAMP-dependent protein kinase catalytic subunit. The impact of the peptide backbone modification was dependent upon its location along the substrate molecule, and seems to be in correlation with the specificity pattern for peptide side chains.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic Chemistry - Volume 38, Issue 5, October 2010, Pages 229–233