Stapled In the ER

Most breast cancer tumors are estrogen receptor (ER) positive, with common therapies, such as tamoxifen, blocking ER activity. Unfortunately, tumors treated with this type of endocrine therapy relapse or recur in nearly half of all cases. It appears that the function of ER is altered such that, while it retains ER expression, it no longer responds to endocrine therapy. Thomas E. Speltz et al, in ACS Chemical Biology, designed a cell-permeable stapled peptide inhibitor and evaluated its ability to block the estrogen receptor. Stapled peptides are held into a certain conformation, or constrained, by side chain linkages. Due to its constrained nature, a stapled peptide has increased stability, both conformational and proteolytic. Using molecular dynamic simulations, Speltz and team designed the peptide called R4K1, that inhibits the ER/coactivator interaction after being taken up by the breast cancer cells. The ER/coactivator interaction is an alpha-helical protein-protein interaction. The addition of arginine residues increased cell-permeability, and may have also enhanced binding affinity, which was seen through a significant increase in hydrogen bonds formed.1 Hopefully R4K1 will pave the way for additional research on stapled peptide inhibitors for the treatment of ER+ breast cancers.

Reference:

  1. T. E. Speltz et al., ACS Chem Biol., 13, 676 (2018).

Related Content:

Endocrine Resistance in Breast Cancer Cells: https://www.pepnet.com/PepTalk/Article/119/Endocrine-Resistance-in-Breast-Cancer-Cells

Past breast cancer features and our products for breast cancer research can be found here: https://www.pepnet.com/site_search.html?query=breast%20cancer

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Denise Karounos

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Denise Karounos joined Peptides International in October 2016. After completing her BS in chemistry from West Virginia University, she spent time as an organic chemist at Bachem Bioscience synthesizing peptides and amino acid derivatives. Denise has experience with both solid and solution-phase peptide synthesis, and has worked under both research and cGMP settings. After completing her MBA from Saint Joseph’s University, Denise transitioned into product management of peptides and amino acid derivatives. In her marketing role, she had many duties including but not limited to product management, market research, creating and producing marketing materials, handling US catalog distribution and customer database, email marketing, quoting and inside sales, sales calls, and coordinating and attending trade conferences. 

At PI, Denise's duties encompass both sales and marketing, bringing to bear her extensive lab and sales support experience. Contact her today and see how Denise can assist you with your peptide research project.