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Degradation of Akt using protein-catalyzed capture agents

Henning, Ryan K. and Varghese, Joseph O. and Das, Samir and Nag, Arundhati and Tang, Grace and Tang, Kevin and Sutherland, Alexander M. and Heath, James R. (2016) Degradation of Akt using protein-catalyzed capture agents. Journal of Peptide Science, 22 (4). pp. 196-200. ISSN 1075-2617. PMCID PMC4883657. doi:10.1002/psc.2858.

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Abnormal signaling of the protein kinase Akt has been shown to contribute to human diseases such as diabetes and cancer, but Akt has proven to be a challenging target for drugging. Using iterative in situ click chemistry, we recently developed multiple protein-catalyzed capture (PCC) agents that allosterically modulate Akt enzymatic activity in a protein-based assay. Here, we utilize similar PCCs to exploit endogenous protein degradation pathways. We use the modularity of the anti-Akt PCCs to prepare proteolysis targeting chimeric molecules that are shown to promote the rapid degradation of Akt in live cancer cells. These novel proteolysis targeting chimeric molecules demonstrate that the epitope targeting selectivity of PCCs can be coupled with non-traditional drugging moieties to inhibit challenging targets.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Nag, Arundhati0000-0002-1328-1695
Heath, James R.0000-0001-5356-4385
Alternate Title:Degradation of Akt Using Protein Catalyzed Capture Agents
Additional Information:© 2016 European Peptide Society and John Wiley & Sons, Ltd. Article first published online: 16 FEB 2016. Manuscript Accepted: 30 DEC 2015. Manuscript Revised: 29 DEC 2015. Manuscript Received: 21 OCT 2015. Funded by: National Cancer Institute. Grant Number: 1U54CA199090-01 Institute for Collaborative Biotechnologies. Grant Number: W911NF-09-0001
Funding AgencyGrant Number
National Cancer Institute1U54CA199090-01
Army Research Office (ARO)W911NF-09-0001
Subject Keywords:click chemistry; protein-catalyzed capture agents; PROTAC; Akt
Issue or Number:4
PubMed Central ID:PMC4883657
Record Number:CaltechAUTHORS:20160222-101242946
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Official Citation:Henning, R. K., Varghese, J. O., Das, S., Nag, A., Tang, G., Tang, K., Sutherland, A. M., and Heath, J. R. (2016) Degradation of Akt using protein-catalyzed capture agents. J. Pept. Sci., 22: 196–200. doi: 10.1002/psc.2858
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64629
Deposited By: Tony Diaz
Deposited On:22 Feb 2016 18:19
Last Modified:06 May 2022 17:27

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