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Modulation of Src Kinase Activity by Selective Substrate Recognition with Pseudopeptidic Cages
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Chemistry (Weinheim an Der Bergstrasse, Germany), Digital.CSIC: Repositorio Institucional del CSIC, Consejo Superior de Investigaciones Científicas (CSIC)
- Publication Year :
- 2021
- Publisher :
- Wiley-Blackwell, 2021.
-
Abstract
- The selective recognition of tyrosine residues in peptides is an appealing approach to inhibiting their tyrosine kinase (TK)‐mediated phosphorylation. Herein, we describe pseudopeptidic cages that efficiently protect substrates from the action of the Src TK enzyme, precluding the corresponding Tyr phosphorylation. Fluorescence emission titrations show that the most efficient cage inhibitors strongly bind the peptide substrates with a very good correlation between the binding constant and the inhibitory potency. Structural insights and additional control experiments further support the proposed mechanism of selective supramolecular protection of the substrates. Moreover, the approach also works in a completely different kinase‐substrate system. These results illustrate the potential of supramolecular complexes for the efficient and selective modulation of TK signaling.<br />How to spare Tyr: The selective recognition of tyrosine residues by pseudopeptidic cages protects the substrates from Src kinase‐promoted phosphorylation. The Tyr kinase‐inhibiting activity of the cages can be satisfactorily explained by the formation of host‐guest complexes. This supramolecular approach represents an appealing alternative to modulating Tyr kinase activity by substrate recognition.
- Subjects :
- cages
tyrosine kinases
Supramolecular chemistry
Hot Paper
Peptide
010402 general chemistry
01 natural sciences
supramolecular chemistry
Catalysis
Substrate Specificity
Tyrosine
Kinase activity
chemistry.chemical_classification
Full Paper
phosphorylation
010405 organic chemistry
Chemistry
Organic Chemistry
General Chemistry
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Protein-Tyrosine Kinases
0104 chemical sciences
src-Family Kinases
Enzyme
peptides
Biophysics
Phosphorylation
Tyrosine kinase
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Chemistry (Weinheim an Der Bergstrasse, Germany), Digital.CSIC: Repositorio Institucional del CSIC, Consejo Superior de Investigaciones Científicas (CSIC)
- Accession number :
- edsair.doi.dedup.....b3fc52a2216ac0068e0c858ef09bfa78