title: Novel hexapeptide interacts with tubulin and microtubules, inhibits Aβ fibrillation, and shows significant neuroprotection.
abstract: Herein, we report a novel hexapeptide, derived from activity dependent neuroprotective protein (ADNP), that spontaneously self-assembles to form antiparallel β-sheet structure and produces nanovesicles under physiological conditions. This peptide not only strongly binds with β-tubulin in the taxol binding site but also binds with the microtubule lattice in vitro as well as in intracellular microtubule networks. Interestingly, it shows inhibition of amyloid fibril formation upon co-incubation with Aβ peptide following an interesting mechanistic pathway and excellent neuroprotection in PC12 cells treated with anti-nerve growth factor (NGF). The potential of this hexapeptide opens up a new paradigm in design and development of novel therapeutics for AD.
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Biswas
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kurkute
authors.affiliation: ‡Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, West Bengal India.
authors.forename: Suraiya
authors.initials: S
authors.lastname: Saleem
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Batakrishna
authors.initials: B
authors.lastname: Jana
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Saswat
authors.initials: S
authors.lastname: Mohapatra
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Mondal
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Anindyasundar
authors.initials: A
authors.lastname: Adak
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Subhajit
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Saha
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Debmalya
authors.initials: D
authors.lastname: Bhunia
authors.affiliation: ‡Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, West Bengal India.
authors.forename: Subhash Chandra
authors.initials: SC
authors.lastname: Biswas
authors.affiliation: †Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.|§Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology Campus, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain; D002470:Cell Survival; D002942:Circular Dichroism; D004353:Drug Evaluation, Preclinical; D006041:Goats; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C000607491:Asn-Ala-Val-Ser-Ile-Gln; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D014404:Tubulin; C075222:amyloid beta-protein (1-42)
keywords: Aβ42 peptide; PC12 cell; microtubule; neuroprotective peptide; tubulin