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Effect of two simultaneous aza-β3-amino acid substitutions on recognition of peptide substrates by cAMP dependent protein kinase catalytic subunit.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2011 Aug; Vol. 39 (4), pp. 133-7. Date of Electronic Publication: 2011 May 07. - Publication Year :
- 2011
-
Abstract
- Peptidomimetic analogs of the hexapeptide RRASVA, containing simultaneously two aza-β(3)-amino acid residues in different positions of this sequence, except for the phosphorylatable serine residue, were synthesized and tested as substrates for the cAMP-dependent protein kinase catalytic subunit. All these peptidomimetics were phosphorylated by the enzyme and this reaction was characterized by the K(m) and k(cat) values as well as by the second-order rate constants k(II). Affinity and reactivity of all peptidomimetics was lower than that for the parent peptide RRASVA. The effect of backbone modification was dependent upon the positions where these two aza-β(3) residues were located, although the sequence of amino acid side groups remained the same in all compounds. It was found that the influence of two backbone modifications in the substrate structure was not described additively, i.e. the effect of each structural alteration was dependent upon the position of the second modification. The results were in agreement with the concept of specificity-determining clusters in the sequence of peptide and peptidomimetic ligands, which predominantly determine the molecular recognition of these ligands by their target sites and therefore serve as major modification points for the design of activity of peptidomimetic ligands.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Binding Sites
Catalytic Domain
Computer Simulation
Kinetics
Peptidomimetics
Phosphorylation
Substrate Specificity
Amino Acids chemistry
Aza Compounds chemistry
Cyclic AMP-Dependent Protein Kinases chemistry
Cyclic AMP-Dependent Protein Kinases metabolism
Peptides chemistry
Peptides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 39
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21683975
- Full Text :
- https://doi.org/10.1016/j.bioorg.2011.04.001