New protein vector ApE1 for targeted delivery of anticancer drugs.
A new chimeric gene ApE1 encoding the receptor-binding domain of the human alpha-fetoprotein fused to a sequence of 22 glutamic acid residues was constructed. A new bacterial producer strain E. coli SHExT7 ApE1 was selected for ApE1 production in a soluble state. A simplified method was developed to purify ApE1 from bacterial biomass. It was shown that the new vector protein selectively interacts with AFP receptors on the tumor cell surface and can be efficiently accumulated in tumor cells. In addition, ApE1 was shown to be stable in storage and during its chemical modification. An increased number of carboxyl groups in the molecule allows the production of cytotoxic compound conjugates with higher drug-loading capacity and enhanced tumor targeting potential.
Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies (Kurchatov NBIC Centre), National Research Centre Kurchatov Institute, Academician Kurchatov Square, 1, Building 348, Moscow 123182, Russia. natpo2002@mail.ru
N V
NV
Pozdniakova
N V
NV
Gorokhovets
N V
NV
Gukasova
A V
AV
Bereznikova
E S
ES
Severin
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004926:Escherichia coli / Q000235:genetics; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D008969:Molecular Sequence Data; D011099:Polyglutamic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D018000:Receptors, Peptide / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C097353:AFP protein, human; D000970:Antineoplastic Agents; D004337:Drug Carriers; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D000509:alpha-Fetoproteins; C042144:alpha-fetoprotein receptor, human; D011099:Polyglutamic Acid; D016650:Fluorescein-5-isothiocyanate