1111791-75-3Relevant academic research and scientific papers
Solid-phase methodology for synthesis of O-alkylated aromatic oligoamide inhibitors of α-helix-mediated protein-protein interactions
Murphy, Natasha S.,Prabhakaran, Panchami,Azzarito, Valeria,Plante, Jeffrey P.,Hardie, Michaele J.,Kilner, Colin A.,Warriner, Stuart L.,Wilson, Andrew J.
, p. 5546 - 5550 (2013/06/27)
Rapid access to rigid rods: A method is described for the synthesis of 3-O-alkylated aromatic oligobenzamide foldamers that could be used for assembly of libraries of α-helix mimetic inhibitors of protein-protein interactions (see scheme; Fmoc=9-fluorenyl
Design, synthesis, and evaluation of an a-helix mimetic library targeting protein-protein interactions
Shaginian, Alex,Whitby, Landon R.,Hong, Sukwon,Hwang, Inkyu,Farooqi, Bilal,et al.
supporting information; experimental part, p. 5564 - 5572 (2009/09/25)
The design and solution-phase synthesis of an α-helix mimetic library as an integral component of a small-molecule library targeting protein - protein interactions are described. The iterative design, synthesis, and evaluation of the candidate α-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 × 20 × 20-mix),where the added subunits are designed to mimic all possible permutation s of the naturally occurring i, i + 4, i + 7 amino acid side chains of an α-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead α-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an α-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.
Controlling curvature in a family of oligoamide α-helix mimetics
Saraogi, Ishu,Incarvito, Christopher D.,Hamilton, Andrew D.
supporting information; experimental part, p. 9691 - 9694 (2009/05/30)
(Figure Presented) Catching up with the curve! The natural curvature found in a majority of a helices has been mimicked in small synthetic oligoamide scaffolds. Differences in hydrogen-bonding patterns in these scaffolds lead to mimetics with varying degrees of curvature in the backbone. This adds another parameter to the structural and functional mimicry of a helices.
