eprintid: 22670 rev_number: 18 userid: 3651 dir: disk0/00/02/26/70 datestamp: 2014-09-15 17:40:17 lastmod: 2016-11-15 14:23:05 status_changed: 2014-09-15 17:40:17 type: thesis_degree succeeds: 21785 metadata_visibility: show contact_email: john.kavouris@gmail.com item_issues_id: thesis_degree_versioning item_issues_id: duplicate_title_21785 item_issues_type: thesis_degree_versioning item_issues_type: duplicate_title item_issues_description: ETD 22670 is using versioning. item_issues_description: Duplicate title to Kavouris, John N-Myristoyltransferase inhibition as a tool for antileishmanial drug discovery: Use in high-throughput, de novo, and piggyback strategies for drug development. Master's Thesis, University of Pittsburgh. item_issues_timestamp: 2014-08-12 06:27:02 item_issues_timestamp: 2014-08-12 06:27:02 item_issues_status: discovered item_issues_status: autoresolved item_issues_count: 1 eprint_status: archive creators_name: Kavouris, John creators_email: jak208@pitt.edu creators_id: JAK208 title: N-Myristoyltransferase inhibition as a tool for antileishmanial drug discovery: Use in high-throughput, de novo, and piggyback strategies for drug development ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: Leishmaniasis, leishmania donovani, visceral leishmaniasis, neglected tropical diseases, N-myristoyltransferase abstract: Leishmaniasis is a disease caused by the Leishmania genus of protozoan parasites, and spread by the phlebotomine genus of sandfly. The disease is caused by at least 20 different species of Leishmania parasites, and manifests itself in three forms: cutaneous, mucocutaneous, and most severely, visceral leishmaniasis. Current chemotherapeutic treatments for leishmaniasis are limited by parasite resistance to existing drugs, highly toxic side effects, and high cost of treatment. As a neglected tropical disease, there has been relatively little research toward new drugs, despite a large need, comprising 1.3m new cases and 20,000-50,000 deaths annually. Fortunately, although there is a wide variety in species causing the disease, visceral leishmaniasis is largely caused by a single species of parasite, Leishmania donovani, greatly simplifying the search for drugs against the most dangerous form of the disease. The whole genome of the species has been sequenced, and many crystal structures of key proteins have been elucidated. Specifically, N-myristoyltransferase (NMT) has emerged as a promising enzyme for target-based antileishmanial drug development, with a wide array of tools available for any level of drug discovery: in silico modeling and docking, enzyme specific assays for protozoan and human isoforms, high throughput in vitro assays against both the parasite itself and infected host cells, and animal models of the disease. However, with L. donovani NMT as a newer target, research has yet to utilize all of these individual elements synergistically with themselves, or with related studies in different parasite species. Combined analysis of these methods can yield a more efficient search for antileishmanials, regardless of screening type. date: 2014-09-15 date_type: published pages: 62 institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Nelson, Scott G. etdcommittee_name: Gold, Barry I. etdcommittee_name: Horne, W. Seth etdcommittee_email: sgnelson@pitt.edu etdcommittee_email: goldbi@pitt.edu etdcommittee_email: horne@pitt.edu etdcommittee_id: SGNELSON etdcommittee_id: GOLDBI etdcommittee_id: HORNE etd_defense_date: 2014-04-25 etd_approval_date: 2014-09-15 etd_submission_date: 2014-06-06 etd_release_date: 2014-09-15 etd_access_restriction: immediate etd_patent_pending: FALSE thesis_type: thesis degree: MS citation: Kavouris, John (2014) N-Myristoyltransferase inhibition as a tool for antileishmanial drug discovery: Use in high-throughput, de novo, and piggyback strategies for drug development. Master's Thesis, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/22670/1/Kavouris_2014.pdf