Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches
Authorized Users Only
2019
Authors
Albert, Lea
Penalver, Alberto
Đoković, Nemanja

Werel, Laura
Hoffarth, Malte
Ružić, Dušan

Xu, Jing
Essen, Lars-Oliver
Nikolić, Katarina

Dou, Yali
Vazquez, Olalla
Article (Published version)

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Show full item recordAbstract
Life relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible-light-responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein-protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue-/green-light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein-binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a mo...lecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators.
Keywords:
azobenzenes / isomerization / peptidomimetics / photochemistry / protein-protein interactionsSource:
Chembiochem, 2019, 20, 11, 1417-1429Publisher:
- Wiley-VCH Verlag GMBH, Weinheim
Funding / projects:
DOI: 10.1002/cbic.201800737
ISSN: 1439-4227
PubMed: 30675988
WoS: 000474071700012
Scopus: 2-s2.0-85065047737
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Institution/Community
PharmacyTY - JOUR AU - Albert, Lea AU - Penalver, Alberto AU - Đoković, Nemanja AU - Werel, Laura AU - Hoffarth, Malte AU - Ružić, Dušan AU - Xu, Jing AU - Essen, Lars-Oliver AU - Nikolić, Katarina AU - Dou, Yali AU - Vazquez, Olalla PY - 2019 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3258 AB - Life relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible-light-responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein-protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue-/green-light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein-binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a molecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators. PB - Wiley-VCH Verlag GMBH, Weinheim T2 - Chembiochem T1 - Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches VL - 20 IS - 11 SP - 1417 EP - 1429 DO - 10.1002/cbic.201800737 ER -
@article{ author = "Albert, Lea and Penalver, Alberto and Đoković, Nemanja and Werel, Laura and Hoffarth, Malte and Ružić, Dušan and Xu, Jing and Essen, Lars-Oliver and Nikolić, Katarina and Dou, Yali and Vazquez, Olalla", year = "2019", abstract = "Life relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible-light-responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein-protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue-/green-light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein-binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a molecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators.", publisher = "Wiley-VCH Verlag GMBH, Weinheim", journal = "Chembiochem", title = "Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches", volume = "20", number = "11", pages = "1417-1429", doi = "10.1002/cbic.201800737" }
Albert, L., Penalver, A., Đoković, N., Werel, L., Hoffarth, M., Ružić, D., Xu, J., Essen, L., Nikolić, K., Dou, Y.,& Vazquez, O.. (2019). Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches. in Chembiochem Wiley-VCH Verlag GMBH, Weinheim., 20(11), 1417-1429. https://doi.org/10.1002/cbic.201800737
Albert L, Penalver A, Đoković N, Werel L, Hoffarth M, Ružić D, Xu J, Essen L, Nikolić K, Dou Y, Vazquez O. Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches. in Chembiochem. 2019;20(11):1417-1429. doi:10.1002/cbic.201800737 .
Albert, Lea, Penalver, Alberto, Đoković, Nemanja, Werel, Laura, Hoffarth, Malte, Ružić, Dušan, Xu, Jing, Essen, Lars-Oliver, Nikolić, Katarina, Dou, Yali, Vazquez, Olalla, "Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches" in Chembiochem, 20, no. 11 (2019):1417-1429, https://doi.org/10.1002/cbic.201800737 . .