Proteolytically Stable Cyclic Decapeptide for Breast Cancer Cell Targeting

• Published in: Journal of medicinal chemistry Vol. 60; no. 12; pp. 4893 - 4903
• Main Authors: Raghuwanshi, Yogita, Etayash, Hashem, Soudy, Rania, Paiva, Igor, Lavasanifar, Afsaneh, Kaur, Kamaljit
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22-06-2017
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carbocyanines - pharmacokinetics; Cell Line, Tumor; Female; Gold; Humans; Immobilized Proteins - chemistry; Immobilized Proteins - metabolism; Mice, Nude; Peptides, Cyclic - administration & dosage; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacokinetics; Proteolysis; Xenograft Model Antitumor Assays
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.7b00163

Starting with a previously reported linear breast cancer targeting decapeptide WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one d-amino acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by the noncancerous cells compared to the linear peptide with two d-amino acids (x and k), and was stable toward proteolytic degradation. When immobilized on gold microcantilever surface, the cyclic peptide was able to capture breast cancer cells specifically and sense samples with ≥25 cancer cells/mL. Animal studies using mice carrying orthotopic breast MDA-MB-231 tumors showed that the cyclic peptide preferentially accumulates in tumor (2 h after injection) and is rapidly cleared from all other organs except kidneys and liver. The study highlights the discovery of a novel proteolytically stable cyclic peptide that can be used for targeted drug delivery or for enumerating circulating breast tumor cells.