Show simple item record

dc.contributor.advisorRobertus, Jon D.en
dc.creatorBai, Yan, 1977-en
dc.date.accessioned2012-02-27T22:09:23Zen
dc.date.available2012-02-27T22:09:23Zen
dc.date.issued2009-12en
dc.date.submittedDecember 2009en
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2009-12-396en
dc.descriptiontexten
dc.description.abstractRicin and Shiga toxin type 1 are potent cytotoxins known as ribosome inhibition proteins, abbreviated RIPs. Proteins of this family shut down protein synthesis by removing a critical adenine in the conserved stem-loop structure of 28S rRNA. Due to its exquisite cytotoxicity, the plant toxin ricin has been used as a biological warfare agent. Although great achievement has been made on ricin research, including catalytic mechanism and structure analysis, there is still no specific treatment available for ricin exposure. In addition, ricin A chain inhibitors may also be useful against the homologous bacterial proteins shiga toxins, which are responsible for dysentery, and diseases related to food poisoning, including hemolytic uremic syndrome. Previous study on RTA inhibitor search has provided a number of substrate analog inhibitors, all of which, however, are weaker inhibitors. Therefore, the goal of this work is to improve the binding affinity of known inhibitors and to discovery new scaffolds for inhibitor discovery and development. In this work, multiple approaches were employed for this purpose, including optimizing known inhibitors and searching new inhibitors by Virtual Drug Screening (VDS) and High Throughput Screening (HTS). A number of new RTA inhibitors were discovered by these strategies, which provide a variety of pharmacophores for RTA inhibitor design, and also added a new line of evidence for VDS as an advanced technology for drug discovery and development.en
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.subjectRIPsen
dc.subjectRicin A chainen
dc.subjectShiga toxinen
dc.subjectInhibitorsen
dc.subjectVirtual screeningen
dc.subjectHigh throughput screeningen
dc.titleProgress in the search for ricin A chain and shiga toxin inhibitorsen
dc.date.updated2012-02-27T22:09:37Zen
dc.identifier.slug2152/ETD-UT-2009-12-396en
dc.description.departmentBiochemistryen
dc.type.genrethesisen
thesis.degree.departmentBiochemistryen
thesis.degree.disciplineBiochemistryen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record