Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Design of Peptide-Based Inhibitor Agent Against Amyloid-Β Aggregation: Molecular Docking, Synthesis and in Vitro Evaluation Publisher Pubmed



Jokar S1 ; Erfani M2 ; Bavi O3 ; Khazaei S4 ; Sharifzadeh M5 ; Hajiramezanali M1 ; Beiki D7 ; Shamloo A8
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Radiation Applications Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
  3. 3. Department of Mechanical and Aerospace Engineering, Shiraz University of Technology, Shiraz, Iran
  4. 4. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Toxicology and Pharmacology, Faculty of Pharmacy
  6. 6. Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran

Source: Bioorganic Chemistry Published:2020


Abstract

Formation of the amyloid beta (Aβ) peptide aggregations represents an indispensable role in appearing and progression of Alzheimer disease. β-sheet breaker peptides can be designed and modified with different amino acids in order to improve biological properties and binding affinity to the amyloid beta peptide. In the present study, three peptide sequences were designed based on the hopeful results of LIAIMA peptide and molecular docking studies were carried out onto the monomer and fibril structure of amyloid beta peptide using AutoDock Vina software. According to the obtained interactions and binding energy from docking, the best-designed peptide (D-GABA-FPLIAIMA) was chosen and synthesized in great yield (%96) via the Fmoc solid-phase peptide synthesis. The synthesis and purity of the resulting peptide were estimated and evaluated by Mass spectroscopy and Reversed-phase high-performance liquid chromatography (RP-HPLC) methods, respectively. Stability studies in plasma and Thioflavin T (ThT) assay were performed in order to measure the binding affinity and in vitro aggregation inhibition of Aβ peptide. The D-GABA-FPLIAIMA peptide showed good binding energy and affinity to Aβ fibrils, high stability (more than 90%) in human serum, and a reduction of 20% in inhibition of the Aβ aggregation growth. Finally, the favorable characteristics of our newly designed peptide make it a promising candidate β-sheet breaker agent for further in vivo studies. © 2020 Elsevier Inc.
Experts (# of related papers)
Other Related Docs