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A Synthetic Loop Replacement Peptide That Blocks Canonical NF-?B Signaling.

ABSTRACT: Aberrant canonical NF-?B signaling is implicated in diseases from autoimmune disorders to cancer. A major therapeutic challenge is the need for selective inhibition of the canonical pathway without impacting the many non-canonical NF-?B functions. Here we show that a selective peptide-based inhibitor of canonical NF-?B signaling, in which a hydrogen bond in the NBD peptide is synthetically replaced by a non-labile bond, shows an about 10-fold increased potency relative to the original inhibitor. Not only is this molecule, NBD2, a powerful tool for dissection of canonical NF-?B signaling in disease models and healthy tissues, the success of the synthetic loop replacement suggests that the general strategy could be useful for discovering modulators of the many protein-protein interactions mediated by such structures.

SUBMITTER: Bruno PA

PROVIDER: S-EPMC5587901 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A Synthetic Loop Replacement Peptide That Blocks Canonical NF-κB Signaling.

Bruno Paul A PA Morriss-Andrews Alex A Henderson Andrew R AR Brooks Charles L CL Mapp Anna K AK

Angewandte Chemie (International ed. in English) 20161028 48

Aberrant canonical NF-κB signaling is implicated in diseases from autoimmune disorders to cancer. A major therapeutic challenge is the need for selective inhibition of the canonical pathway without impacting the many non-canonical NF-κB functions. Here we show that a selective peptide-based inhibitor of canonical NF-κB signaling, in which a hydrogen bond in the NBD peptide is synthetically replaced by a non-labile bond, shows an about 10-fold increased potency relative to the original inhibitor. ...[more]

PMID: 27791341

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