title: C-Terminal Fragment, Aβ32-37, Analogues Protect Against Aβ Aggregation-Induced Toxicity.
abstract: Amyloid-β aggregation is a major etiological phenomenon in Alzheimer's disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Aβ aggregation. Taking the hexapeptide fragment, Aβ32-37, as lead, more than 40 new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Aβ toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Aβ aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (1) showed complete mitigation of Aβ toxicity in the cell culture assay at 2 μM. In the ThT fluorescence assay, upon incubation of Aβ with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research , Sector 67, S.A.S Nagar 160 062, Punjab India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Bansal
authors.affiliation: Department of Microbial Biotechnology, Panjab University , Sector 14, Chandigarh 160 014, India.
authors.forename: Indresh Kumar
authors.initials: IK
authors.lastname: Maurya
authors.affiliation: International Center for Genetic Engineering and Biotechnology , Aruna Asif Ali Marg, New Delhi 110 067, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Yadav
authors.affiliation: International Center for Genetic Engineering and Biotechnology , Aruna Asif Ali Marg, New Delhi 110 067, India.
authors.forename: Chaitanya Kumar
authors.initials: CK
authors.lastname: Thota
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research , Sector 67, S.A.S Nagar 160 062, Punjab India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research , Sector 67, S.A.S Nagar 160 062, Punjab India.
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
authors.affiliation: International Center for Genetic Engineering and Biotechnology , Aruna Asif Ali Marg, New Delhi 110 067, India.
authors.forename: Virander Singh
authors.initials: VS
authors.lastname: Chauhan
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research , Sector 67, S.A.S Nagar 160 062, Punjab India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D066329:Protein Aggregates / Q000502:physiology*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates
keywords: Alzheimer’s disease; Aβ aggregation; MTT; TEM; ThT fluorescence assay; hexapeptide