scholarly journals Allosteric Inhibition of Parkinson’s-Linked LRRK2 by Constrained Peptides

2021 ◽  
Author(s):  
Leah G. Helton ◽  
Ahmed Soliman ◽  
Felix von Zweydorf ◽  
Michalis Kentros ◽  
Jascha T. Manschwetus ◽  
...  
Keyword(s):  
Allosteric Inhibition ◽  
Constrained Peptides

scholarly journals Small and Simple, yet Sturdy: Conformationally Constrained Peptides with Remarkable Properties

2021 ◽  
Vol 22 (4) ◽  
pp. 1611
Author(s):  
Krištof Bozovičar ◽  
Tomaž Bratkovič
Keyword(s):  
Chemical Space ◽  
Structure Optimization ◽  
Peptide Chain ◽  
Conformationally Constrained ◽  
Drug Candidates ◽  
Conformational Constraints ◽  
Macrocyclic Peptides ◽  
Constrained Peptides ◽  
Sheer Size

The sheer size and vast chemical space (i.e., diverse repertoire and spatial distribution of functional groups) underlie peptides’ ability to engage in specific interactions with targets of various structures. However, the inherent flexibility of the peptide chain negatively affects binding affinity and metabolic stability, thereby severely limiting the use of peptides as medicines. Imposing conformational constraints to the peptide chain offers to solve these problems but typically requires laborious structure optimization. Alternatively, libraries of constrained peptides with randomized modules can be screened for specific functions. Here, we present the properties of conformationally constrained peptides and review rigidification chemistries/strategies, as well as synthetic and enzymatic methods of producing macrocyclic peptides. Furthermore, we discuss the in vitro molecular evolution methods for the development of constrained peptides with pre-defined functions. Finally, we briefly present applications of selected constrained peptides to illustrate their exceptional properties as drug candidates, molecular recognition probes, and minimalist catalysts.

A study of the allosteric inhibition of HCV RNA-dependent RNA polymerase and implementing virtual screening for the selection of promising dual-site inhibitors with low resistance potential

2016 ◽  
Vol 37 (4) ◽  
pp. 341-354 ◽  
Author(s):  
Nasser S. M. Ismail ◽  
Heba S. A. Elzahabi ◽  
Peter Sabry ◽  
Fady N. Baselious ◽  
Andrew Samy AbdelMalak ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Rna Polymerase ◽  
Hcv Rna ◽  
Rna Dependent Rna Polymerase ◽  
Allosteric Inhibition ◽  
Low Resistance ◽  
Dual Site ◽  
Selection Of
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