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Tytuł:
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Delivery of Non-Native Cargo into Mammalian Cells Using Anthrax Lethal Toxin.
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Autorzy:
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Rabideau AE; Massachusetts Institute of Technology , Department of Chemistry, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Pentelute BL; Massachusetts Institute of Technology , Department of Chemistry, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
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Źródło:
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ACS chemical biology [ACS Chem Biol] 2016 Jun 17; Vol. 11 (6), pp. 1490-501. Date of Electronic Publication: 2016 May 02.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review
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Język:
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English
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Imprint Name(s):
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Original Publication: Washington, D.C. : American Chemical Society, c2006-
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MeSH Terms:
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Antigens, Bacterial/*chemistry
Bacterial Toxins/*chemistry
Drug Carriers/*chemistry
Proteins/*metabolism
Aminoacyltransferases/chemistry ; Animals ; Bacterial Proteins/chemistry ; Cell Line, Tumor ; Cysteine Endopeptidases/chemistry ; Cytosol/metabolism ; Humans ; Membrane Transport Proteins/metabolism ; Protein Transport ; Proteins/chemistry
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Substance Nomenclature:
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0 (Antigens, Bacterial)
0 (Bacterial Proteins)
0 (Bacterial Toxins)
0 (Drug Carriers)
0 (Membrane Transport Proteins)
0 (Proteins)
0 (anthrax toxin)
EC 2.3.2.- (Aminoacyltransferases)
EC 2.3.2.- (sortase A)
EC 3.4.22.- (Cysteine Endopeptidases)
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Entry Date(s):
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Date Created: 20160409 Date Completed: 20170919 Latest Revision: 20170919
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Update Code:
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20240104
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DOI:
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10.1021/acschembio.6b00169
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PMID:
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27055654
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The intracellular delivery of peptide and protein therapeutics is a major challenge due to the plasma membrane, which acts as a barrier between the extracellular environment and the intracellular milieu. Over the past two decades, a nontoxic PA/LFN delivery platform derived from anthrax lethal toxin has been developed for the transport of non-native cargo into the cytosol of cells in order to understand the translocation process through a protective antigen (PA) pore and to probe intracellular biological functions. Enzyme-mediated ligation using sortase A and native chemical ligation are two facile methods used to synthesize these non-native conjugates, inaccessible by recombinant technology. Cargo molecules that translocate efficiently include enzymes from protein toxins, antibody mimic proteins, and peptides of varying lengths and non-natural amino acid compositions. The PA pore has been found to effectively convey over 30 known cargos other than native lethal factor (LF; i.e., non-native) with diverse sequences and functionalities on the LFN transporter protein. All together these studies demonstrated that non-native cargos must adopt an unfolded or extended conformation and contain a suitable charge composition in order to efficiently pass through the PA pore. This review provides insight into design parameters for the efficient delivery of new cargos using PA and LFN.