Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide

Abstract Artemisinin, a natural product isolated from Artemisia annua L. , shows a unique anti-cancer activity by an iron dependent mechanism. Artemisinin was covalently conjugated to a transferrin-receptor targeting peptide, HAIYPRH that binds to a cavity on the surface of transferrin receptor. Thi...

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Bibliographic Details
Published in:Cancer letters 2009-02, Vol.274 (1), p.33-39
Main Authors: Oh, Steve, Kim, Byung Ju, Singh, Narendra P, Lai, Henry, Sasaki, Tomikazu
Format: Article
Language:English
Subjects:
Anti-cancer
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Artemisia - chemistry
Artemisinin
Artemisinins - chemical synthesis
Artemisinins - chemistry
Artemisinins - pharmacology
Binding sites
Cancer
Cells, Cultured
Cytotoxicity
Free radicals
Hematology, Oncology and Palliative Medicine
Humans
Leukemia
Leukemia - drug therapy
Leukemia - metabolism
Leukemia - pathology
Leukocytes - drug effects
Leukocytes - metabolism
Peptide
Peptide Fragments - chemical synthesis
Peptide Fragments - chemistry
Peptide Fragments - pharmacology
Peptides
Proteins
Receptors, Transferrin - metabolism
Recombinant Fusion Proteins - pharmacology
Transferrin - metabolism
Transferrin receptor
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Summary:Abstract Artemisinin, a natural product isolated from Artemisia annua L. , shows a unique anti-cancer activity by an iron dependent mechanism. Artemisinin was covalently conjugated to a transferrin-receptor targeting peptide, HAIYPRH that binds to a cavity on the surface of transferrin receptor. This enables artemisinin to be co-internalized with receptor-bound transferrin. The iron released from transferrin can activate artemisinin to generate toxic radical species to kill cells. The artemisinin-peptide conjugates showed potent anti-cancer activity against Molt-4 leukemia cells with a significantly improved cancer/normal cells selectivity.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2008.08.031