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Targeted Nanoswitchable Inhibitors of Protein–Protein Interactions Involved in Apoptosis
Author(s) -
Nevola Laura,
Varese Monica,
MartínQuirós Andrés,
Mari Giacomo,
Eckelt Kay,
Gorostiza Pau,
Giralt Ernest
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800647
Subject(s) - protein–protein interaction , peptide , drug , target protein , computational biology , p53 protein , chemistry , drug delivery , drug discovery , biophysics , microbiology and biotechnology , nanotechnology , apoptosis , biology , biochemistry , pharmacology , materials science , gene
Progress in drug delivery is hampered by a lack of efficient strategies to target drugs with high specificity and precise spatiotemporal regulation. The remote control of nanoparticles and drugs with light allows regulation of their action site and dosage. Peptide‐based drugs are highly specific, non‐immunogenic, and can be designed to cross the plasma membrane. In order to combine target specificity and remote control of drug action, here we describe a versatile strategy based on a generalized template to design nanoswitchable peptides that modulate protein–protein interactions upon light activation. This approach is demonstrated to promote photomodulation of two important targets involved in apoptosis (the interactions Bcl‐xL–Bak and MDM2–p53), but can be also applied to a large pool of therapeutically relevant protein–protein interactions mediated by α‐helical motifs. The template can be adjusted using readily available information about hot spots (residues contributing most to the binding energy) at the protein–protein interface of interest.