Poster Presentation 2014 International Biophysics Congress

Tripeptides - importance of amino acid composition on amyloid Aβ-peptide aggregation (#632)

Katarina Siposova 1 , Man H. Viet 2 , Mai S. Li 2 , Zuzana Bednarikova 1 3 , Andrea Antosova 1 , Truc T. Nguyen 4 , Zuzana Gazova 1
  1. Department of Biophysics, Institute of Experimental Physics, Kosice, Slovakia
  2. Institute of Physics, Polish Academy of Sciences, Warsaw, Poland
  3. Department of Biochemistry, P.J. Safarik University, Kosice, Slovakia
  4. Institute for Computational Science and Technology, Ho Chi Minh City, Vietnam

The aggregation of the Aβ-peptide into oligomers or fibrils is implicated as a key process associated with progression of Alzheimer’s disease [1]. Compounds that inhibit amyloid aggregation may prove their useful as therapeutic agents for the prevention or treatment of Alzheimer’s disease.
In our study using in silico approach we examined the binding of all possible three-amino acid peptides (8000 tripeptides in total) to 6Aβ9−40 amyloid fibrils. The docking method and the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were used to calculate the binding affinity and mode of tripeptides. It was shown that tripeptides prefer to bind to hydrophobic regions of 6Aβ9−40 fibrils. The tightest binding was detected for tripeptides containing Proline and aromatic amino acids. The ability of selected tripeptides characterized different binding properties (the most effective binders, non-bind and weak-bind tripeptides) to influence the amyloid Aβ-peptide fibrils was tested also using experimental techniques (ThT assay, AFM). The significant reduction of amyloid aggregates was observed for tripeptides with Proline and Tryptophan.
Theoretical simulations and in vitro experiments confirmed importance of amino acid composition of tripeptides. The presence of cyclic amino acid Proline and aromatic amino acid Tryptophan is crucial for their tight binding to Aβ fibrils as well as for significant anti-amyloid ability.
Acknowledgement: This work was supported by grants VEGA 0181, No 2011/ 01/B/NZ1/01622, ESF 26110230097, APVV 0171-10.

  1. Hamley, I. W. Angew. Chem., Int. Ed. Engl. 2007, 46, 8128