Modulation of Src Kinase Activity by Selective Substrate Recognition with Pseudopeptidic Cages

Overview

Journal Chemistry

Specialty Chemistry

Date 2021 Apr 27

PMID 33904620

Citations 3

Authors

Lucia Tapia

Naiara Solozabal

Jordi Sola

Yolanda Perez

W Todd Miller

Ignacio Alfonso

Affiliations

Soon will be listed here.

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.

Citing Articles

Molecular Recognition of Tyrosine-Containing Polypeptides with Pseudopeptidic Cages Unraveled by Fluorescence and NMR Spectroscopies.

Solozabal N, Tapia L, Sola J, Perez Y, Alfonso I Bioconjug Chem. 2023; 34(12):2345-2357.

PMID: 38078839 PMC: 10859922. DOI: 10.1021/acs.bioconjchem.3c00455.

Substrate Protection in Controlled Enzymatic Transformation of Peptides and Proteins.

Zhao Y Chembiochem. 2021; 22(17):2680-2687.

PMID: 34058051 PMC: 8453913. DOI: 10.1002/cbic.202100217.

Modulation of Src Kinase Activity by Selective Substrate Recognition with Pseudopeptidic Cages.

Tapia L, Solozabal N, Sola J, Perez Y, Miller W, Alfonso I Chemistry. 2021; 27(37):9542-9549.

PMID: 33904620 PMC: 8362067. DOI: 10.1002/chem.202100990.

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