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dc.contributor.authorTharappel, Anil Mathew
dc.contributor.authorLi, Zhong
dc.contributor.authorLi, Hongmin
dc.date.accessioned2022-08-05T00:27:28Z
dc.date.available2022-08-05T00:27:28Z
dc.date.issued2022-02-08
dc.identifier.citationTharappel, A. M., Li, Z., & Li, H. (2022). Inteins as Drug Targets and Therapeutic Tools. Frontiers in Molecular Biosciences, 9.en_US
dc.identifier.doi10.3389/fmolb.2022.821146
dc.identifier.urihttp://hdl.handle.net/10150/665547
dc.description.abstractMultidrug-resistant pathogens are of significant concern in recent years. Hence new antifungal and anti-bacterial drug targets are urgently needed before the situation goes beyond control. Inteins are polypeptides that self-splice from exteins without the need for cofactors or external energy, resulting in joining of extein fragments. Inteins are present in many organisms, including human pathogens such as Mycobacterium tuberculosis, Cryptococcus neoformans, C. gattii, and Aspergillus fumigatus. Because intein elements are not present in human genes, they are attractive drug targets to develop antifungals and antibiotics. Thus far, a few inhibitors of intein splicing have been reported. Metal-ions such as Zn2+ and Cu2+, and platinum-containing compound cisplatin inhibit intein splicing in M. tuberculosis and C. neoformans by binding to the active site cysteines. A small-molecule inhibitor 6G-318S and its derivative 6G-319S are found to inhibit intein splicing in C. neoformans and C. gattii with a MIC in nanomolar concentrations. Inteins have also been used in many other applications. Intein can be used in activating a protein inside a cell using small molecules. Moreover, split intein can be used to deliver large genes in experimental gene therapy and to kill selected species in a mixed population of microbes by taking advantage of the toxin-antitoxin system. Furthermore, split inteins are used in synthesizing cyclic peptides and in developing cell culture model to study infectious viruses including SARS-CoV-2 in the biosafety level (BSL) 2 facility. This mini-review discusses the recent research developments of inteins in drug discovery and therapeutic research.en_US
dc.description.sponsorshipDivision of Intramural Research, National Institute of Allergy and Infectious Diseasesen_US
dc.language.isoenen_US
dc.publisherFrontiers Media SAen_US
dc.rightsCopyright © 2022 Tharappel, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subjectinteinen_US
dc.subjectinhibitoren_US
dc.subjectdrug targeten_US
dc.subjecttherapeutic toolen_US
dc.subjectanti-microbialen_US
dc.titleInteins as Drug Targets and Therapeutic Toolsen_US
dc.typeArticleen_US
dc.identifier.eissn2296-889X
dc.contributor.departmentDepartment of Pharmacology and Toxicology, College of Pharmacy, The University of Arizonaen_US
dc.contributor.departmentBIO5 Institute, The University of Arizonaen_US
dc.identifier.journalFrontiers in Molecular Biosciencesen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.pii10.3389/fmolb.2022.821146
dc.source.journaltitleFrontiers in Molecular Biosciences
dc.source.volume9
refterms.dateFOA2022-08-05T00:27:29Z


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Copyright © 2022 Tharappel, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Except where otherwise noted, this item's license is described as Copyright © 2022 Tharappel, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).