Recent Developments in 14–3–3 Stabilizers for Regulating Protein–Protein Interactions: An Update DOI
Yucheng Tian, Lan Li,

Liuyi Wu

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

14–3–3 proteins play a crucial role in the regulation of protein–protein interactions, impacting various cellular processes and disease mechanisms. Recent advancements have led to development stabilizers that enhance binding clients, presenting promising therapeutic potentials. This perspective provides an updated overview latest developments field stabilizers, with focus on their design, synthesis, biological evaluation. We discuss structural basis for interaction between ligands, highlighting key modifications affinity selectivity. Additionally, we explore applications across major areas such as cancer, metabolic disorders, neurodegenerative diseases. By summarizing recent research findings technological advancements, this aims shed light current state stabilizer outline future directions optimizing these compounds effective agents.

Language: Английский

Harnessing the 14-3-3 protein–protein interaction network DOI Creative Commons
Paulo Pitasse-Santos,

Isaac Hewitt-Richards,

Malsha D. Abeywickrama Wijewardana Sooriyaarachchi

et al.

Current Opinion in Structural Biology, Journal Year: 2024, Volume and Issue: 86, P. 102822 - 102822

Published: April 28, 2024

Protein–protein interactions (PPIs) play a critical role in cellular signaling and represent interesting targets for therapeutic intervention. 14-3-3 proteins integrate many via PPIs are frequently implicated disease, making them intriguing drug targets. Here, we review the recent advances field. It will discuss roles within cell, elucidation of their expansive interactome, complex mechanisms that underpin function. In addition, significant development molecular glues target PPIs. particular, it focus on novel discovery methodologies have delivered selective, potent, drug-like molecules could open new avenues precision tools medicines.

Language: Английский

Citations

10
Rapid flow-based synthesis of post-translationally modified peptides and proteins: a case study on MYC's transactivation domain DOI Creative Commons
Elyse T. Williams, Kevin Schiefelbein, Matthias Schuster

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(23), P. 8756 - 8765

Published: Jan. 1, 2024

Automated flow peptide synthesis (AFPS) gives access to peptides and proteins with post-translational modifications (PTMs) enables investigation of PTM-mediated regulation, was used study the PTM-dependence MYC:Bin1 interaction.

Language: Английский

Citations

4
Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms DOI Open Access

Lina Yin,

Tingting Niu, Ling Li

et al.

Chinese Herbal Medicines, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The mechanism of action traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused exploring the mechanisms active components acting single targets. However, it is insufficient to explain complex by which these in treat diseases. In recent years, emergence molecular glues (MGs) theory provided new strategies address this issue. MGs are small molecules that can promote interactions between proteins at their interface. characteristic establish connections diverse protein structures, thereby enabling a chemically-mediated proximity effect triggers wide spectrum biological functions. Natural products result billions years evolutionary processes natural environment. Thus, extensive structural diversity renders them rich source MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known immunosuppressants cyclosporin A (CsA) tacrolimus (FK506), as well anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, advancement technologies propelling discovery novel from products. we primarily summarize growing variety origins reported categorize based chemical types. Moreover, main sources promises provide perspective for elucidation behind efficiency TCM. summary, review aims insights could potentially influence modern drug development.

Language: Английский

Citations

0
Traversing the drug discovery landscape using native mass spectrometry DOI Creative Commons
Hannah M. Britt, Carol V. Robinson

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 91, P. 102993 - 102993

Published: Feb. 1, 2025

Language: Английский

Citations

0
Recent Developments in 14–3–3 Stabilizers for Regulating Protein–Protein Interactions: An Update DOI
Yucheng Tian, Lan Li,

Liuyi Wu

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

14–3–3 proteins play a crucial role in the regulation of protein–protein interactions, impacting various cellular processes and disease mechanisms. Recent advancements have led to development stabilizers that enhance binding clients, presenting promising therapeutic potentials. This perspective provides an updated overview latest developments field stabilizers, with focus on their design, synthesis, biological evaluation. We discuss structural basis for interaction between ligands, highlighting key modifications affinity selectivity. Additionally, we explore applications across major areas such as cancer, metabolic disorders, neurodegenerative diseases. By summarizing recent research findings technological advancements, this aims shed light current state stabilizer outline future directions optimizing these compounds effective agents.

Language: Английский

Citations

0