Design and synthesis of novel N-terminal peptides of integrin and aminopeptidase are new finding for anticancer activity.

[Display omitted] • N-terminal modified peptides preferentially bind with anionic lipid bilayer membrane, which could be used for bio-analysis. • The anti-cancer activities of both peptides were evaluated against the four cancer cells and normal cells namely, Hep-2, HepG2, MCF-7, A375, and Vero. • The peptide is largely unordered to ordered structure and non-toxic towards normal cell. • In-silico studies suggested that the peptides have good binding interactions with the proteins (PDB ID: 2W3L, 5FC4, and 5GWK). The short peptides, containing the amino acid sequence asparagine-glycine-arginine (NGR) and arginine-glycine-aspartic acid (RGD), possess the strong binding ability to N (APN/CD13) aminopeptidase receptor and integrin proteins involved in antitumor properties are overexpressed. A novel short N-terminal modified hexapeptides P1 and P2 was designed and synthesized using the Fmoc-chemistry solid phase peptide synthesis protocol. Notably, the cytotoxicity of the MTT assay demonstrated the viability of normal and cancer cells up to lower peptide concentrations. Interestingly, both peptides show good anticancer activities against the four cancer cells and normal cells namely, Hep-2, HepG2, MCF-7, A375, and Vero and compared with standard drugs, doxorubicin and paclitaxel. Additionally, in silico studies were applied to predict the binding sites and binding orientation of the peptides for potential anticancer targets. Steady-state fluorescence measurements showed that peptide P1 exhibits preferential interactions with POPC/POPG anionic bilayers rather than the zwitterionic POPC lipid bilayers and peptide P2 , did not show any preferential interaction with lipids bilayers. But impressively, peptide P2 shows anticancer activity due to the NGR/RGD motif. Circular dichroism studies demonstrated that the peptide's secondary structure changes only minimally upon binding to the anionic lipid bilayers. [ABSTRACT FROM AUTHOR]