Publications by authors named "Isabella A Riha"

Traditional small molecule drugs often target protein activity directly, but challenges arise when proteins lack suitable functional sites. An alternative approach is targeted protein degradation (TPD), which directs proteins to cellular machinery for proteolytic degradation. Recent studies have identified additional E3 ligases suitable for TPD, expanding the potential of this approach.

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Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation.

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Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. This expansion will broaden the scope of potential protein targets, accommodating those with varying subcellular localizations and expression patterns.

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In this issue of Cell Chemical Biology, Chang et al. report that a PCNA-targeting bioPROTAC, an engineered E3 ligase linked to a PCNA-binding peptide, has superior pharmacological effects over inhibition of PCNA. Their findings demonstrate the feasibility of translating bioPROTACs from a concept to a candidate therapeutic modality.

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Article Synopsis
  • Chemists are actively searching for new covalent organic framework (COF) linkages to enhance material properties and structures.
  • A new strategy has been developed using HPO as a bifunctional catalyst to create amine-linked COFs from common amine and aldehyde linkers.
  • The resulting amine-linked COFs are more effective than their imine counterparts in promoting Knoevenagel condensation due to their better basicity and stability.
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