scholarly journals Structural Re-engineering of the α-Helix Mimetic JY-1-106 into Small Molecules: Disruption of the Mcl-1-Bak-BH3 Protein-Protein Interaction with 2,6-Di-Substituted Nicotinates

ChemMedChem ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. 827-833 ◽  
Author(s):  
Brandon Drennen ◽  
Jacob A. Scheenstra ◽  
Jeremy L. Yap ◽  
Lijia Chen ◽  
Maryanna E. Lanning ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Α Helix

Development of small molecules to target the IgE:FcεRI protein–protein interaction in allergies

2013 ◽  
Vol 5 (12) ◽  
pp. 1423-1435 ◽  
Author(s):  
Lucy D Smith ◽  
Robin J Leatherbarrow ◽  
Alan C Spivey
Keyword(s):  
Small Molecules ◽  
Protein Interaction ◽  
Protein Protein Interaction

scholarly journals Methods for addressing the protein-protein interaction between histone deacetylase 6 and ubiquitin

2017 ◽  
Author(s):  
Carolina dos S. Passos ◽  
Nathalie Deschamps ◽  
Yun Choi ◽  
Robert E. Cohen ◽  
Remo Perozzo ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Stress Response ◽  
Small Molecules ◽  
Histone Deacetylase ◽  
Protein Interaction ◽  
Potential Role ◽  
Histone Deacetylase 6 ◽  
Protein Protein Interaction ◽  
Binding Function

AbstractHistone deacetylase 6 (HDAC6) is a cytoplasmic HDAC isoform able to remove acetyl groups from cellular substrates such as α-tubulin. In addition to the two deacetylase domains, HDAC6 has a C-terminal zinc-finger ubiquitin (Ub)-binding domain (ZnF-UBP) able to recognize free Ub. HDAC6-Ub interaction is thought to function in regulating the elimination of misfolded proteins during stress response through the aggresome pathway. Small molecules inhibiting deacetylation by HDAC6 were shown to reduce aggresomes, but the interplay between HDAC6 catalytic activity and Ub-binding function is not fully understood. Here we describe two methods to measure the HDAC6-Ub interaction in vitro using full-length HDAC6. Both methods were effective for screening inhibitors of the HDAC6-Ub protein-protein interaction independently of the catalytic activity. Our results suggest a potential role for the HDAC6 deacetylase domains in modulating HDAC6-Ub interaction. This new aspect of HDAC6 regulation can be targeted to address the roles of HDAC6-Ub interaction in normal and disease conditions.

scholarly journals Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein–Protein Interaction

Biochemistry ◽  
2017 ◽  
Vol 56 (12) ◽  
pp. 1768-1784 ◽  
Author(s):  
Degang Liu ◽  
David Xu ◽  
Min Liu ◽  
William Eric Knabe ◽  
Cai Yuan ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Interaction ◽  
Hot Spots ◽  
Cooperative Binding ◽  
Protein Protein Interaction

Aromatic Oligoamide Foldamers with a “Wet Edge” as Inhibitors of the α-Helix-Mediated p53-hDM2 Protein-Protein Interaction

2013 ◽  
Vol 2013 (17) ◽  
pp. 3504-3512 ◽  
Author(s):  
Panchami Prabhakaran ◽  
Anna Barnard ◽  
Natasha S. Murphy ◽  
Colin A. Kilner ◽  
Thomas A. Edwards ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Α Helix

scholarly journals Protein-Protein Interaction Disruptors of the YAP/TAZ-TEAD Transcriptional Complex

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6001
Author(s):  
Ajaybabu V. Pobbati ◽  
Brian P. Rubin
Keyword(s):  
Transcription Factors ◽  
Small Molecules ◽  
Protein Interaction ◽  
Hydrophobic Residues ◽  
Common Features ◽  
Protein Protein Interaction ◽  
Pharmacokinetic Properties ◽  
Hydrophobic Portion ◽  
Transcriptional Complex ◽  
And Function

The identification of protein-protein interaction disruptors (PPIDs) that disrupt the YAP/TAZ-TEAD interaction has gained considerable momentum. Several studies have shown that YAP/TAZ are no longer oncogenic when their interaction with the TEAD family of transcription factors is disrupted. The transcriptional co-regulator YAP (its homolog TAZ) interact with the surface pockets of TEADs. Peptidomimetic modalities like cystine-dense peptides and YAP cyclic and linear peptides exploit surface pockets (interface 2 and interface 3) on TEADs and function as PPIDs. The TEAD surface might pose a challenge for generating an effective small molecule PPID. Interestingly, TEADs also have a central pocket that is distinct from the surface pockets, and which small molecules leverage exclusively to disrupt the YAP/TAZ-TEAD interaction (allosteric PPIDs). Although small molecules that occupy the central pocket belong to diverse classes, they display certain common features. They are flexible, which allows them to adopt a palmitate-like conformation, and they have a predominant hydrophobic portion that contacts several hydrophobic residues and a small hydrophilic portion that faces the central pocket opening. Despite such progress, more selective PPIDs that also display favorable pharmacokinetic properties and show tolerable toxicity profiles are required to evaluate the feasibility of using these PPIDs for cancer therapy.

scholarly journals Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

2016 ◽  
Vol 15 (8) ◽  
pp. 533-550 ◽  
Author(s):  
Duncan E. Scott ◽  
Andrew R. Bayly ◽  
Chris Abell ◽  
John Skidmore
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Protein Interaction ◽  
Protein Protein Interaction

scholarly journals Exploring novel strategies for AIDS protozoal pathogens: α-helix mimetics targeting a key allosteric protein–protein interaction in C. hominis thymidylate synthase-dihydrofolate reductase (TS-DHFR)

MedChemComm ◽  
2013 ◽  
Vol 4 (9) ◽  
pp. 1247-1256 ◽  
Author(s):  
W. Edward Martucci ◽  
Johanna M. Rodriguez ◽  
Melissa A. Vargo ◽  
Matthew Marr ◽  
Andrew D. Hamilton ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Protein Interaction ◽  
Thymidylate Synthase ◽  
Opportunistic Infections ◽  
Molecular Target ◽  
Bifunctional Enzyme ◽  
Cryptosporidium Hominis ◽  
Protein Protein Interaction ◽  
Helix Mimetics ◽  
Α Helix

The bifunctional enzyme TS–DHFR from Cryptosporidium hominis is a molecular target for design of antiparasitic therapies for AIDS-related opportunistic infections.

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