jm200750x_si_001.pdf (718.85 kB)
Proteolytically Stable Cancer Targeting Peptides with High Affinity for Breast Cancer Cells
journal contribution
posted on 2016-02-22, 15:51 authored by Rania Soudy, Avneet Gill, Tara Sprules, Afsaneh Lavasanifar, Kamaljit KaurCancer 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 18 that we developed previously, here we report three novel
analogues of 18 that are proteolytically stable and display
better (up to 3.5-fold) affinity profiles for breast cancer cells
compared to 18. The design strategy involved replacement
of two or three amino acids in the sequence of 18 with d-residues or β3-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.