Format

Send to

Choose Destination
ChemMedChem. 2019 Jan 8;14(1):100-106. doi: 10.1002/cmdc.201800647. Epub 2018 Dec 10.

Targeted Nanoswitchable Inhibitors of Protein-Protein Interactions Involved in Apoptosis.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, 08028, Barcelona, Spain.
2
Institute for Bioengineering of Catalonia (IBEC), Barcelona, 08028, Spain.
3
University of Bologna, Bologna, 40126, Italy.
4
Network Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain.
5
Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, 08010, Spain.
6
University of Barcelona (UB), Barcelona, 080280, Spain.

Abstract

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.

KEYWORDS:

helical structures; optopharmacology; peptide engineering; photoswitchable peptides; protein-protein interactions

PMID:
30380184
DOI:
10.1002/cmdc.201800647

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center