Structure-Based Design of Small Peptide Ligands to Inhibit Early-Stage Protein Aggregation Nucleation

2020 ◽  
Vol 60 (6) ◽  
pp. 3304-3314 ◽  
Author(s):  
Avinash Mishra ◽  
Rohit Bansal ◽  
Shravan Sreenivasan ◽  
Rozaleen Dash ◽  
Srishti Joshi ◽  
...  
2005 ◽  
pp. 63-83 ◽  
Author(s):  
Guangquan Wang ◽  
Jeffrey R. Salm ◽  
Patrick V. Gurgel ◽  
Ruben G. Carbonell

RSC Advances ◽  
2015 ◽  
Vol 5 (82) ◽  
pp. 67093-67101 ◽  
Author(s):  
Yuping Wei ◽  
Jiandong Xu ◽  
Liang Zhang ◽  
Yankai Fu ◽  
Xia Xu

Small peptide ligands which were designed based on the interactions with human immunoglobulin G (IgG) using the molecular simulations, can offer a potential alternative for mAb purification with elution condition at pH 9 and pH 3.


2019 ◽  
Vol 5 (10) ◽  
pp. eaax5108 ◽  
Author(s):  
Dafni C. Delivoria ◽  
Sean Chia ◽  
Johnny Habchi ◽  
Michele Perni ◽  
Ilias Matis ◽  
...  

Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer’s and Parkinson’s diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date. We generated a combinatorial library of ~200 million drug-like, cyclic peptides and rapidly screened it for aggregation inhibitors against the amyloid-β peptide (Aβ42), linked to Alzheimer’s disease. Through this procedure, we identified more than 400 macrocyclic compounds that efficiently reduce Aβ42 aggregation and toxicity in vitro and in vivo. Finally, we applied a combination of deep sequencing and mutagenesis analyses to demonstrate how this system can rapidly determine structure-activity relationships and define consensus motifs required for bioactivity.


2017 ◽  
Vol 89 (17) ◽  
pp. 9322-9329 ◽  
Author(s):  
Manjeet Kumar ◽  
Yuning Hong ◽  
David C. Thorn ◽  
Heath Ecroyd ◽  
John A. Carver

2005 ◽  
Vol 33 (4) ◽  
pp. 548-550 ◽  
Author(s):  
B.J. Tabner ◽  
S. Turnbull ◽  
N.J. Fullwood ◽  
M. German ◽  
D. Allsop

By means of an ESR spin-trapping method, we have shown that Aβ (amyloid β), α-synuclein and various toxic forms of the prion protein all appear to generate H2O2in vitro. A fundamental molecular mechanism underlying the pathogenesis of cell death in several different neurodegenerative diseases could be the direct production of H2O2 during the early stages of protein aggregation.


2012 ◽  
Vol 21 (14) ◽  
pp. 3173-3192 ◽  
Author(s):  
Isabel Lastres-Becker ◽  
Ayse Ulusoy ◽  
Nadia G. Innamorato ◽  
Gurdal Sahin ◽  
Alberto Rábano ◽  
...  

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