In this work, we developed new peptide conjugates with natural amino imidazole compounds for targeting over-expressed receptors in breast tumor cells. We first designed nine different conjugates and examined their binding interactions with fibroblast growth factor receptor 2 kinase domain and its gate-keeper mutant V564F using docking studies. Results indicated that upon conjugation with the peptides, the binding affinities were increased compared to the neat amino-imidazole compounds. Molecular dynamics simulations were then conducted to determine the stability of the receptor-ligand complexes. MMGBSA studies further revealed that coulombic interactions played a significant role in enhancing binding interactions. Quantum chemical simulations were carried out using turbomole to determine the changes in hydrogen donor/ acceptor capabilities upon binding with the peptides. Based on the results obtained from computational studies, we then synthesized two of the most optimal conjugates and examined their binding affinities with those receptor proteins using SPR analysis, followed by examining interactions with breast cancer cells. Our results indicated that the peptide conjugates may be potentially developed for targeting tumor cells with specificity.

Design and development of peptide conjugates of amino-imidazoles for targeting tumor cells

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