Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide.
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.
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Steve
S
Oh
Byung Ju
BJ
Kim
Narendra P
NP
Singh
Henry
H
Lai
Tomikazu
T
Sasaki
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D019306:Artemisia / Q000737:chemistry; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011990:Receptors, Transferrin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014168:Transferrin / Q000378:metabolism
D000970:Antineoplastic Agents; D037621:Artemisinins; D010446:Peptide Fragments; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D014168:Transferrin; C031327:artemisinin