title: The receptor binding fragment of alpha-fetoprotein is a promising new vector for the selective delivery of antineoplastic agents.
abstract: The alpha-fetoprotein (AFP) binding protein, a putative AFP receptor, is a tumour marker that is present on the surfaces of malignant cells. AFP enters cells through receptor-mediated endocytosis. The recombinant C-terminal fragment of AFP (AFP-3BC, which consists of amino acid residues 473-596) was obtained by the expression in Escherichia coli. AFP-3BC was shown to be bound specifically to the AFP putative receptor on tumour cells and accumulated by endocytosis in these cells in a similar manner to that of full-length human AFP. In lymphocytes, the binding and endocytosis of AFP-3BC were absent. Thus, the AFP receptor binding site was shown experimentally to be located within the AFP-3BC sequence. A conjugate of synthesised AFP-3BC with the antitumour antibiotic doxorubicin (DOX-AFP-3BC) demonstrated high antitumour activity in vitro. Thus, AFP-3BC can be used successfully as a vector for the targeted selective delivery of drugs into tumour cells.
authors.affiliation: NBIC Centre, National Research Centre Kurchatov Institute, Moscow 117638, Russian Federation. galinapo@gmail.com
authors.forename: Galina A
authors.initials: GA
authors.lastname: Posypanova
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Makarov
authors.forename: Mariya V
authors.initials: MV
authors.lastname: Savvateeva
authors.forename: Anastasiya V
authors.initials: AV
authors.lastname: Bereznikova
authors.forename: Evgeny S
authors.initials: ES
authors.lastname: Severin
mesh_terms: D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C097353:AFP protein, human; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; C042144:alpha-fetoprotein receptor, human; D004317:Doxorubicin