Amyloid detection and inhibition
     

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Amyloid detection and inhibition

Molecular Modeling and Lead Discovery

Many neurodegenerative diseases in humans result from protein misfolding and aggregation. Protein misfolding is thought to be the leading cause of Alzheimer's disease, Parkinson's disease, Huntington's disease, Creutzfeldt-Jakob disease, cystic fibrosis, Gaucher's disease and many other degenerative and neurodegenerative disorders which are collectively known as amyloid disorders.

OTAVA’s scientists in collaboration with researchers from the Institute of Molecular Biology and Genetics are studying protein aggregation and developing the amyloid-sensitive fluorescent dyes as well as designing specific chemical inhibitors of protein aggregation.

 

                          OTAVA offers the following contract research services:                            

 

Amyloid detection:

  1. Development of fluorescent amyloid-sensitive dyes to detect different protein fibrillization products (i.e. mature fibrils, amorphous aggregates, oligomeric intermediates etc.) and monitor aggregation reaction with:
    • required spectral characteristics (excitation/emission wavelength);
    • increased sensitivity to your target protein;
  2. Development of fluorescent detection kits and analysis protocols based on the kits.

Selected publications by OTAVA & collaborators in the area of AMYLOID DETECTION:

  • Kovalska V, Chernii S, Losytskyy M, Dovbii Y, Tretyakova I, Czerwieniec R, Chernii V, Yarmoluk S, Volkov S (2016) b-ketoenole dyes: synthesis and study as fluorescent sensors for protein amyloid aggregates. Dyes and Pigments 132:274-281.
  • Kuperman MV, Chernii SV, Losytskyy MYu, Kryvorotenko DV, Derevyanko NO, Slominskii YuL, Kovalska VB, Yarmoluk SM (2015) Trimethine cyanine dyes as fluorescent probes for amyloid fibrils: The effect of N,N'-substituents. Analytical Biochemistry 484:9-17.
  • Kovalska VB, Losytskyy MY, Tolmachev OI, Slominskii YL, Segers-Nolten GMJ, Subramaniam V, Yarmoluk SM (2012) Tri- and pentamethine cyanine dyes for fluorescent detection of α-synuclein oligomeric aggregates. J Fluoresc 22(6):1441-1448.

 

Amyloid inhibition:

Evaluation of compounds affecting the amyloid aggregation of your target protein. It could include:

  1. Screening of compounds of different chemical classes;
  2. Modeling of aggregated protein-ligand complexes;
  3. Chemical optimization of the lead compounds.

Selected publications by OTAVA & collaborators in the area of AMYLOID INHIBITION:

  • Kovalska V, Chernii S, Cherepanov V, Losytskyy M, Chernii V, Varzatskii O, Naumovets A, Yarmoluk S. The impact of binding of macrocyclic metal complexes on amyloid fibrillization of insulin and lysozyme. J Mol Recognit. (2017 doi: 10.1002/jmr.2622)
  • Kovalska V, Cherepanov V, Losytskyy M, Chernii S, Senenko A, Chernii V, Tretyakova I, Yarmoluk S, Volkov S (2014) Anti-fibrillogenic properties of phthalocyanines: Effect of the out-of-plane ligands. Bioorg Med Chem 22(24):6918-6923
  • Inshyn DI, Kovalska VB, Losytskyy MY, Slominskii YL, Tolmachev OI, Yarmoluk SM (2014) Development of a quantitative structure activity relations (QSAR) model to guide the design of fluorescent dyes for detecting amyloid fibrils. Biotech and Histochem 89(1):1-7

 

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