ChemInform Abstract: Design and Synthesis of Thienylpyridyl Garlands as Non-Peptidic Alpha Helix Mimetics and Potential Protein-Protein Interactions Disruptors.

ChemInform ◽  
2011 ◽  
Vol 42 (52) ◽  
pp. no-no
Author(s):  
Marcella De Giorgi ◽  
Anne Sophie Voisin-Chiret ◽  
Jana Sopkova-de Oliveira Santos ◽  
Filomena Corbo ◽  
Carlo Franchini ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Alpha Helix ◽  
Protein Protein Interactions ◽  
Design And Synthesis ◽  
Helix Mimetics

Design and synthesis of thienylpyridyl garlands as non-peptidic alpha helix mimetics and potential protein–protein interactions disruptors

Tetrahedron ◽  
2011 ◽  
Vol 67 (34) ◽  
pp. 6145-6154 ◽  
Author(s):  
Marcella De Giorgi ◽  
Anne Sophie Voisin-Chiret ◽  
Jana Sopková-de Oliveira Santos ◽  
Filomena Corbo ◽  
Carlo Franchini ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Alpha Helix ◽  
Protein Protein Interactions ◽  
Design And Synthesis ◽  
Helix Mimetics

scholarly journals Synthesis of a Bcl9 Alpha-Helix Mimetic for Inhibition of PPIs by a Combination of Electrooxidative Phenol Coupling and Pd-Catalyzed Cross Coupling

Catalysts ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 340 ◽  
Author(s):  
Martin Vareka ◽  
Benedikt Dahms ◽  
Mario Lang ◽  
Minh Hao Hoang ◽  
Melanie Trobe ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Alpha Helix ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Protein Protein Interactions ◽  
Interaction Sites ◽  
Cross Coupling Reactions ◽  
Helix Mimetics ◽  
Leaving Groups ◽  
Metal Catalyzed

Teraryl-based alpha-helix mimetics have resulted in efficient inhibitors of protein-protein interactions (PPIs). Extending the concept to even longer oligoarene systems would allow for the mimicking of even larger interaction sites. We present a highly efficient synthetic modular access to quateraryl alpha-helix mimetics, in which, at first, two phenols undergo electrooxidative dehydrogenative cross-coupling. The resulting 4,4′-biphenol is then activated by conversion to nonaflates, which serve as leaving groups for iterative Pd-catalyzed Suzuki-cross-coupling reactions with suitably substituted pyridine boronic acids. This work, for the first time, demonstrates the synthetic efficiency of using both electroorganic as well as transition-metal catalyzed cross-coupling in the assembly of oligoarene structures.

Characterization of aggregated morphologies derived from mono- and bis-arylbenzamides – potential alpha-helix mimetics

2017 ◽  
Vol 41 (15) ◽  
pp. 7417-7423
Author(s):  
Oleg V. Kulikov ◽  
Yulia V. Sevryugina ◽  
Arshad Mehmood ◽  
Ishu Saraogi
Keyword(s):  
Protein Interactions ◽  
Self Assembly ◽  
Alpha Helix ◽  
Side Chains ◽  
Protein Protein Interactions ◽  
Alkyl Side Chains ◽  
Helix Mimetics

We report here the synthesis and self-assembly studies of a family of benzamide backbone oligomers bearing various alkyl side chains (e.g., isopropyl, isobutyl, and 2-ethylpentyl), which are potential alpha-helix mimetics capable of disrupting protein–protein interactions.

scholarly journals Rational Design and Synthesis of Right-Handed d-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions

2020 ◽  
Vol 85 (16) ◽  
pp. 10552-10560
Author(s):  
Peng Sang ◽  
Yan Shi ◽  
Pirada Higbee ◽  
Minghui Wang ◽  
Sami Abdulkadir ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rational Design ◽  
Protein Protein Interactions ◽  
Design And Synthesis

The Development of a Modular Synthesis of Teraryl-Based α-Helix Mimetics as Potential Inhibitors of Protein–Protein Interactions

Synlett ◽  
2014 ◽  
Vol 25 (09) ◽  
pp. 1202-1214 ◽  
Author(s):  
Rolf Breinbauer ◽  
Melanie Trobe ◽  
Martin Peters ◽  
Sebastian Grimm
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Modular Synthesis ◽  
Helix Mimetics ◽  
Α Helix ◽  
Potential Inhibitors

Protein–Protein Interactions Affect Alpha Helix Stability in Crowded Environments

2015 ◽  
Vol 119 (7) ◽  
pp. 2956-2967 ◽  
Author(s):  
Bryanne Macdonald ◽  
Shannon McCarley ◽  
Sundus Noeen ◽  
Alan E. van Giessen
Keyword(s):  
Protein Interactions ◽  
Alpha Helix ◽  
Protein Protein Interactions ◽  
Helix Stability ◽  
Crowded Environments

scholarly journals Computational and experimental studies of plasmodium falciparum protein PfAMA1 domain-II loop dynamics: implications in PfAMA1-PfRON2 binding event

2021 ◽  
Author(s):  
Suman Sinha ◽  
Anamika Biswas ◽  
Jagannath Mondal ◽  
Kalyaneswar Mandal
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Experimental Studies ◽  
Alpha Helix ◽  
Dynamics Simulation ◽  
Malarial Parasite ◽  
Titration Calorimetry ◽  
Protein Protein Interactions ◽  
Human Red Blood Cells ◽  
Developed Nations

Protein-protein interactions are interesting targets for various drug discovery campaigns. One such promising and therapeutically pertinent protein-protein complex is PfAMA1-PfRON2, which is involved in malarial parasite invasion into human red blood cells. A thorough understanding of the interactions between these macromolecular binding partners is absolutely necessary to design better therapeutics to fight against the age-old disease affecting mostly under-developed nations. Although crystal structures of several PfAMA1-PfRON2 complexes have been solved to understand the molecular interactions between these two proteins, the mechanistic aspects of the domain II loop-PfRON2 association is far from clear. The current work investigates a crucial part of the recognition event; i.e., how the domain II loop of PfAMA1 exerts its effect on the alpha helix of the PfRON2, thus influencing the overall kinetics of this intricate recognition phenomenon. To this end, we have conducted thorough computational investigation of the dynamics and free energetics of domain II loop closing processes using molecular dynamics simulation. The computational results are validated by systematic alanine substitutions of the PfRON2 peptide helix. The subsequent evaluation of the binding affinity of Ala-substituted PfRON2 peptide ligands by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) provides a rank of the relative importance of the residues in context. Our combined (computational and experimental) investigation has revealed that the domain II loop of PfAMA1 is in fact responsible for arresting the PfRON2 molecule from egress, K2027 and D2028 of PfRON2 being the determinant residues for the capturing event. Our study provides a comprehensive understanding of the molecular recognition event between PfAMA1 and PfRON2, specifically in the post binding stage, which potentially can be utilized for drug discovery against malaria.

α-Helix mimetics as inhibitors of protein–protein interactions

2008 ◽  
Vol 36 (6) ◽  
pp. 1414-1417 ◽  
Author(s):  
Ishu Saraogi ◽  
Andrew D. Hamilton
Keyword(s):  
Protein Interactions ◽  
First Generation ◽  
Side Chain ◽  
Protein Protein Interactions ◽  
Substitution Pattern ◽  
Pathological Conditions ◽  
Synthetic Accessibility ◽  
Helix Mimetics ◽  
Viable Approach ◽  
Α Helix

The inhibition of protein–protein interactions using small molecules is a viable approach for the treatment of a range of pathological conditions that result from a malfunctioning of these interactions. Our strategy for the design of such agents involves the mimicry of side-chain residues on one face of the α-helix; these residues frequently play a key role in mediating protein–protein interactions. The first-generation terphenyl scaffold, with a 3,2′,2″-substitution pattern, is able to successfully mimic key helix residues and disrupt therapeutically relevant interactions, including the Bcl-XL–Bak and the p53–hDM2 (human double minute 2) interactions that are implicated in cancer. The second- and third-generation scaffolds have resulted in greater synthetic accessibility and more drug-like character in these molecules.

scholarly journals Design and Synthesis of a New Orthogonally Protected Glutamic Acid Analog and Its Use in the Preparation of High Affinity Polo-like Kinase 1 Polo-box Domain – binding Peptide Macrocycles

2021 ◽  
Author(s):  
David Hymel ◽  
Kohei Tsuji ◽  
Robert A. Grant ◽  
Ramesh M. Chingle ◽  
Dominique L. Kunciw ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Binding Peptide ◽  
Design And Synthesis ◽  
High Affinity ◽  
Acid Analog ◽  
Therapeutic Development

Targeting protein – protein interactions (PPIs) has emerged as important area of discovery for anticancer therapeutic development. In the case of phospho-dependent PPIs, such as the polo-like kinase 1 (Plk1)...

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