{"id":7236,"date":"2017-08-02T09:50:59","date_gmt":"2017-08-02T13:50:59","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?p=7236"},"modified":"2017-08-02T09:50:59","modified_gmt":"2017-08-02T13:50:59","slug":"phosphonium-tethered-terpyridine-metal-complexes-as-g4-dna-binders","status":"publish","type":"post","link":"https:\/\/web.uri.edu\/riinbre\/phosphonium-tethered-terpyridine-metal-complexes-as-g4-dna-binders\/","title":{"rendered":"Phosphonium Tethered Terpyridine Metal Complexes as G4-DNA Binders"},"content":{"rendered":"

Investigator:<\/span><\/strong>\u00a0<\/a>Chin Hin Leung, Rhode Island College<\/span><\/span><\/p>\n

Scientific Theme:<\/span><\/strong>\u00a0Cancer<\/span><\/span><\/p>\n

Abstract:<\/span><\/strong>\u00a0<\/span><\/span>Guanine-rich DNA quadruplex (G4-DNA) is a form of DNA generally believed to play a crucial role in telomerase activity and certain gene regulations, and has been studied as a potential target for anti-cancer agents. Transition metal containing complexes with a planar environment around the metal center, such as complexes of Cu2+<\/sup>, Pd2+<\/sup> or Pt2+<\/sup> with tolyl-terpyridine(ttpy), are well established G4-DNA binders. It is proposed that such complexes effectively bind to G4 DNA through the duo mechanism of \u03c0-stacking and additional nucleobase binding at the Cu\/Pd\/Pt metal center.<\/span><\/p>\n

Phosphoniums have been known to travel well across cell membranes due to their lipophilicity, and their cytotoxicity could have more pronounced effects on cancerous cells because of the increased cell potential in cancer cells. We are interested in how the addition of a phosphonium tether will affect the DNA-binding properties of the aforementioned planar, transition metal complexes. The tether might bequeath additional, possibly favorable properties to these metal complexes, such as higher membrane permeability and additional mechanisms for cytotoxicity.<\/span><\/p>\n

The proposed research will study the G4-DNA binding abilities of transition metal complexes with the general motif [M-ttpy-PR3]+, where M is a transition metal center such as Cu2+<\/sup>, Pd2+<\/sup> or Pt2+<\/sup>, and -PR3<\/sub>+ <\/sup>is a phosphonium bearing various R groups. We seek to build a library through variation of the transition metal M and the phosphonium R groups, and characterize the G4-DNA binding abilities of this library of compounds through various analyses including fluorescent resonance energy transfer (FRET) melting analysis, G4 Fluorescent Intercalator Displacement (G4-FID) assay, UV-visible spectrometry, circular dichroism and gel electrophoresis. We will address how the phosphonium tether will affect G4-DNA binding, specifically the degree of quadruplex stabilization, the selectivity of the binding (among the different forms of G4-DNA, against double stranded and other non-quadruplex forms of DNA), and the possible modes of binding. This study will contribute to the field of knowledge in G4-DNA and its potential as target for cancer therapy<\/span><\/p>\n

Human Health Relevance:<\/span><\/strong>\u00a0<\/span><\/span>Traditional metal-based anticancer agents are widely used but suffer from severe side effects. The proposed research will shed light on new strategies to target cancer cells by binding to the less common quadruplex DNA. This could lead to more specific targeting of cancer cells, and the potential benefits include less severe side-effects and effectiveness against drug-resistant tumors.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Investigator:\u00a0Chin Hin Leung, Rhode Island College Scientific Theme:\u00a0Cancer Abstract:\u00a0Guanine-rich DNA quadruplex (G4-DNA) is a form of DNA generally believed to play a crucial role in telomerase activity and certain gene regulations, and has been studied as a potential target for anti-cancer agents. Transition metal containing complexes with a planar environment around the metal center, such […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[96],"tags":[],"class_list":["post-7236","post","type-post","status-publish","format-standard","hentry","category-research"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/posts\/7236","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=7236"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/posts\/7236\/revisions"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=7236"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/categories?post=7236"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/tags?post=7236"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}