title: Novel conjugation of tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) with monomethyl auristatin E for efficient antitumor drug delivery.
abstract: Monomethyl auristatin E (MMAE) is conjugated with TNF-related apoptosis-inducing ligand (TRAIL) via a linker that is stable in extracellular fluid, while it is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the antimitotic mechanism of MMAE. The TRAIL-MMAE conjugate is a conceptually viable therapeutic strategy with improved in vitro antitumor activity, cell circle arrest and specific accumulation in tumor to treat TRAIL-resistant tumors.
authors.affiliation: Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Pan
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wang
authors.forename: Zhang-Ming
authors.initials: ZM
authors.lastname: Xie
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Li
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Tang
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Xu
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Naranmandura
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002403:Cathepsins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009842:Oligopeptides; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D002403:Cathepsins; C495575:monomethyl auristatin E
keywords: antitumor agents; biomedical applications; drug delivery; protein modifications; protein-protein interactions