Abstract
Microtubule is one of the most studied targets in cancer research. Stabilizing and destabilizing of the microtubule by targeting its building block tubulin are common mechanisms of microtubule targeting agents. Cancer associates inversely with Alzheimer’s disease (AD). So the rate of developing AD is significantly slower in patients with cancer and vice versa. Amyloid-β (Aβ) peptide inhibits tubulin polymerization and induces apoptotic death of cancer cells. We studied the interactions of Aβ with tubulin using protein-protein docking and MD simulation. Aβ bond to the vicinity of the vinblastine binding site and interacted with the H6-H7 loop. Interaction of Aβ with H6-H7 loop blocked nucleotide exchange and may be attributed as a possible reason for blocking of tubulin polymerization. We designed new Aβ-based peptidic inhibitors of tubulin using visual inspection and alanine scanning method. P1 (FRHYHHFFELV) and P9 (HYHHF) bound efficiently to tubulin and also interacted with the H6-H7 loop. Obtained results indicated that proposed peptides could potentially inhibit nucleotide exchange as Aβ.
Communicated by Ramaswamy H. Sarma
Acknowledgments
The authors thank the support of Vice-chancellor for Research, Hamadan University of Medical Sciences, Iran. We thank Research and Technology Vice-chancellor of Hamadan University of Medical Sciences for financial support. The study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 9405062577).
Disclosure statement
Authors declare no conflict of interest.