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Houston KM, Melvin AT, Woss GS, et al. Development of β-Hairpin Peptides for the Measurement of SCF-Family E3 Ligase Activity in Vitro via Ornithine Ubiquitination. ACS Omega. 2017;2(3):1198-1206doi: 10.1021/acsomega.7b00109.
Houston, K. M., Melvin, A. T., Woss, G. S., Fayer, E. L., Waters, M. L., & Allbritton, N. L. (2017). Development of β-Hairpin Peptides for the Measurement of SCF-Family E3 Ligase Activity in Vitro via Ornithine Ubiquitination. ACS omega, 2(3), 1198-1206. https://doi.org/10.1021/acsomega.7b00109
Houston, Kaiulani M, et al. "Development of β-Hairpin Peptides for the Measurement of SCF-Family E3 Ligase Activity in Vitro via Ornithine Ubiquitination." ACS omega vol. 2,3 (2017): 1198-1206. doi: https://doi.org/10.1021/acsomega.7b00109
Houston KM, Melvin AT, Woss GS, Fayer EL, Waters ML, Allbritton NL. Development of β-Hairpin Peptides for the Measurement of SCF-Family E3 Ligase Activity in Vitro via Ornithine Ubiquitination. ACS Omega. 2017 Mar 31;2(3):1198-1206. doi: 10.1021/acsomega.7b00109. Epub 2017 Mar 29. PMID: 28393136; PMCID: PMC5377275.
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ACS Omega. 2017 Mar 31;2(3):1198-1206. doi: 10.1021/acsomega.7b00109. Epub 2017 Mar 29.

Development of β-Hairpin Peptides for the Measurement of SCF-Family E3 Ligase Activity in Vitro via Ornithine Ubiquitination.

ACS omega

Kaiulani M Houston, Adam T Melvin, Gregery S Woss, Effrat L Fayer, Marcey L Waters, Nancy L Allbritton

Affiliations

  1. Department of Chemistry, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
  2. Cain Department of Chemical Engineering, Louisiana State University , Baton Rouge, Louisiana 70803, United States.
  3. Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, United States; Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, United States.

PMID: 28393136 PMCID: PMC5377275 DOI: 10.1021/acsomega.7b00109

Abstract

Regulation of the ubiquitin-proteasome system (UPS) to treat select types of cancer has become a popular area of drug discovery research. The FDA approval of proteasome inhibitors Bortezomib and Carfilzomib in the treatment of multiple myeloma has led to an increased need for chemical reporters capable of detecting and quantifying protein ubiquitination and the activity of members of the UPS including E3 ubiquitin ligases and the proteasome in the tumor cells of the patients. One limitation of peptide-based reporters is their rapid degradation in the cellular environment by cytosolic peptidases. Conversely, β-hairpin "protectides" exhibit a pronounced secondary structure that significantly increases their lifetime under cellular conditions. The goal of this work was to develop a family of novel, ornithine-rich protectides that could act as primary degrons serving as substrates for in vitro ubiquitination. The fluorescent peptide-based reporters were demonstrated to be highly resistant to degradation in multiple myeloma cell lysates. The most stable β-hairpin primary degron, containing a single ornithine residue at the N-terminus, OWRWR [Ac-OWVRVpGO(FAM)WIRQ-NH

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