title: Preparation and evaluation of a CD13/APN-targeting and hydrolase-resistant conjugate that comprises pingyangmycin and NGR motif-integrated apoprotein.
abstract: We have chemically synthesized NGR-LDP-PYM, a novel CD13/aminopeptidase (APN)-targeting and hydrolase-resistant conjugate by cross-linking of the antitumor antibiotic pingyangmycin (bleomycin A5 , PYM) to an engineered NGR motif-integrated apoprotein (NGR-LDP) with a noncleavable linker. This protein-drug conjugate not only basically retains the original properties of PYM but also can specifically deliver PYM to the CD13/APN-expressing tumor cells. Furthermore, the resulting conjugate exhibits more resistance to hydrolysis of recombinant human bleomycin hydrolase than parental PYM. These results may be useful for improving the therapeutic efficacy of PYM and have implications in the treatment of PYM-refractory and CD13/APN-overexpressing tumors.
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors: Bin
authors: B
authors: Li
authors: Yan-Bo
authors: YB
authors: Zheng
authors: Dian-Dong
authors: DD
authors: Li
authors: Yong-Su
authors: YS
authors: Zhen
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000911:Antibodies, Monoclonal; D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism; D001761:Bleomycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D001059:Apoproteins; D011993:Recombinant Fusion Proteins; D001761:Bleomycin; C025703:bleomycetin; D006867:Hydrolases; D000626:Aminopeptidases; D018826:CD13 Antigens
keywords: CD13/APN-targeting; NGR motif-integrated apoprotein; cancer; drug design; drug metabolizing enzymes; pingyangmycin/bleomycin A5 conjugate; resistance