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The signal peptide as a new target for drug design

Journal

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 30, Issue 10, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2020.127115

Keywords

CADA; CD4; ER; Hereditary diseases; Inhibitor; Protein; Sec61; Signal peptide; Sortilin; Translocation

Funding

  1. National Institutes of Health (NIH) [1R15 GM120659-01]

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Many current and potential drug targets are membrane-bound or secreted proteins that are expressed and transported via the Sec61 secretory pathway. They are targeted to translocon channels across the membrane of the endoplasmic reticulum (ER) by signal peptides (SPs), which are temporary structures on the N-termini of their nascent chains. During translation, such proteins enter the lumen and membrane of the ER by a process known as co-translational translocation. Small molecules have been found that interfere with this process, decreasing protein expression by recognizing the unique structures of the SPs of particular proteins. The SP may thus become a validated target for designing drugs for numerous disorders, including certain hereditary diseases.

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