scholarly journals Development of Allosteric BRAF Peptide Inhibitors Targeting the Dimer Interface of BRAF

2019 ◽  
Vol 14 (7) ◽  
pp. 1471-1480 ◽  
Author(s):  
Amber Y. Gunderwala ◽  
Anushri A. Nimbvikar ◽  
Nicholas J. Cope ◽  
Zhijun Li ◽  
Zhihong Wang
Keyword(s):  
Peptide Inhibitors ◽  
Dimer Interface

Peptide Inhibitors of Aspartic Proteinases with Hydroxyethylene Isostere Replacement of Peptide Bond. II. Preparation of Pseudotetrapeptides Derived from Diastereoisomeric 5-Amino-2-benzyl-4-hydroxy-6-phenylhexanoic Acids

1998 ◽  
Vol 63 (4) ◽  
pp. 541-548 ◽  
Author(s):  
Jaroslav Litera ◽  
Jan Weber ◽  
Ivana Křížová ◽  
Iva Pichová ◽  
Jan Konvalinka ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Peptide Bond ◽  
Peptide Inhibitors ◽  
Aspartic Proteinases ◽  
Hiv 1

Twelve pseudotetrapeptides, Boc-NHCH(CH2Ph)CH(OH)CH2CH(CH2Ph) CO-Xaa-Phe-NH2 9-11, were prepared by [(benzotriazol-1-yl)oxy]tris(dimethylamino)phosphonium hexafluorophosphate-mediated couplings of diastereoisomeric O-silylated (2R or 2S,4R or 4S,5S)-2-benzyl-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenylhexanoic acids 1 with dipeptides H-Xaa-Phe-NH2 (Xaa = Gln, Glu(OBzl) or Ile) 3-5, followed by O-deprotection. Pseudotetrapeptides 9-11 were tested for inhibition of aspartic proteinases secreted by Candida albicans and C. tropicalis. The level of inhibition of both yeast proteinases was very low, contrasting with the nanomolar IC50 values obtained for inhibition of HIV-1 proteinase.

scholarly journals Designed Cell-Penetrating Peptide Inhibitors of Amyloid-beta Aggregation and Cytotoxicity

2020 ◽  
Vol 1 (2) ◽  
pp. 100014 ◽  
Author(s):  
Anja Henning-Knechtel ◽  
Sunil Kumar ◽  
Cecilia Wallin ◽  
Sylwia Król ◽  
Sebastian K.T.S. Wärmländer ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Peptide Inhibitors ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

scholarly journals Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming

2021 ◽  
Author(s):  
Daniel J. Ford ◽  
Nisharnthi M. Duggan ◽  
Sarah E. Fry ◽  
Jorge Ripoll-Rozada ◽  
Stijn M. Agten ◽  
...  
Keyword(s):  
Genetic Code ◽  
Cyclic Peptide ◽  
Peptide Inhibitors ◽  
Mrna Display

scholarly journals Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 198
Author(s):  
Lijun Lang ◽  
Alberto Perez
Keyword(s):  
Bayesian Inference ◽  
Virtual Screening ◽  
Statistical Mechanics ◽  
Small Molecules ◽  
Rational Design ◽  
Driving Forces ◽  
Peptide Inhibitors ◽  
Atomistic Simulations ◽  
Binding Mechanism ◽  
Intrinsically Disordered

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).

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