2013 Volume 7 Issue 5 Pages 209-220
The plasma membrane presents a remarkable barrier for the delivery of peptide and nucleic acid based drugs to the inside of cells. This restraint in the path of their development as therapeutic agents can be offset by their conjugation to cell penetrating peptides (CPPs) that can lead to an improved pharmacological profile. In this context, conformational behavior of Vimentin Tubulin Binding Site (TBS) peptide, Vim-TBS (58-81), was investigated for its acknowledged cell penetrating properties along with Trans-activating Tat (48-60) peptide and a pro-apoptogenic peptide of p21/WAFI protein (p10). Also, the fusion peptides Vim-TBS (58-81)-p10 & Tat (48-60)-p10 were studied using molecular mechanics (MM) and molecular dynamics (MD) based strategies. MM results revealed formation of stable α-helix like secondary structures in Vim-TBS (58-81), Tat (48-60) and p10 peptides. In water, three peptides adopted either a helical structure or a random conformation; the stability of either of the two states being governed by the formation of polar contacts with the solvent. The fusion peptides formed helical structures after MD simulations but the structure obtained for the fusion peptide, Vim-TBS-p10 is relatively better characterized in terms of its amphipathic nature with a hydrophilic face formed by the positively charged residues facilitating a better interaction of this fusion peptide with the membrane as compared to that of Tat-p10 peptide. This is the first report on the conformational characteristics of the Vim-TBS (58-81) peptide and the fusion peptide, Vim-TBS (58-81)-p10. The results presented here are significant for their potential role in guiding and facilitating the future efforts of designing peptide based cell penetrating drugs.