Proteolytically Stable Cancer Targeting Peptides with High Affinity for Breast Cancer Cells
2016-02-22T15:51:17Z (GMT) by
Cancer cell targeting peptides have emerged as a highly efficient approach for selective delivery of chemotherapeutics and diagnostics to different cancer cells. However, the use of α-peptides in pharmaceutical applications is hindered by their enzymatic degradation and low bioavailability. Starting with a 10-mer α-peptide <b>18</b> that we developed previously, here we report three novel analogues of <b>18</b> that are proteolytically stable and display better (up to 3.5-fold) affinity profiles for breast cancer cells compared to <b>18</b>. The design strategy involved replacement of two or three amino acids in the sequence of <b>18</b> with d-residues or β<sup>3</sup>-amino acids. Such replacement maintained the specificity for cancer cells (MDA-MB-435, MDA-MB-231, and MCF-7) with low affinity for control noncancerous cells (MCF-10A and HUVEC), showed an increase in secondary structure, and rendered the analogues completely stable to human serum and liver homogenate from mice. The three analogues are potentially safe with minimal cellular toxicity and are efficient targeting moieties for specific drug delivery to breast cancer cells. The strategy used here may be adapted to develop peptide analogues that will target other cancer cell types.
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