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Proteolytically stable cancer targeting peptides with high affinity for breast cancer cells.

Abstract：

: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 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 β(3)-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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Soudy R,Gill A,Sprules T,Lavasanifar A,Kaur K

doi

10.1021/jm200750x

subject

Has Abstract

pub_date

2011-11-10 00:00:00

pages

7523-34

issue

21

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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