Selective therapy with minor groove binders
type: CreativeWork
description: Over the past five years, the University of Strathclyde has developed extremely potent anti-bacterial molecules known as minor groove binding agents (MGB) which intrinsic helicity allows binding to the minor groove of DNA. These molecules were effective in vivo, non-toxic and showed activity and selectivity against Gram positive bacteria. Whilst such selectivity is an advantage, an extension of activity of such agents towards Gram negative organisms and eventually targeting cancer cells would be valuable. Since the biological properties of such minor groove bonders are related to the chemical feature, this aim could be achieved by modifying the structure of the tail group only. The MPhil project involved the synthesis of a small number of selected minor groove binders differing in their tail groups (Boc protected, OAc protected, guanidine, cyano alkene, nitro alkene) but bearing the same fluorescent head group ((E)-4-(3-methoxystyryl)benzyl). The yield of the coupling reaction between the head group and the pyrrole-pyrrole core linked with a protected tail group (Boc or OAc) was improved up to two- to five- fold, using propane phosphonic acid anhydride as a mild reagent. These MGBs were then evaluated for anti-bacterial and anti-cancer drug activity in screens available at the Strathclyde Institute of Pharmaceutical and Biological Sciences (SIPBS). They were tested against Gram negative E. coli, against Gram positive Staph. aureus and against the fibroblast hamster cell line V79, in order to evaluate respectively their anti-bacterial activity and their toxicity. The penetration of these synthesized molecules into bacteria and cells was observed under microscopy in order to assess the structural features that could lead to a potential anti-bacterial and/or anti-cancer molecule if nuclear permeation occurs. Almost all MGBs tested permeate into Gram positive bacteria, but not all of them showed an anti-bacterial activity. These results were consistent with earlier expe…
abstract: Over the past five years, the University of Strathclyde has developed extremely potent anti-bacterial molecules known as minor groove binding agents (MGB) which intrinsic helicity allows binding to the minor groove of DNA. These molecules were effective in vivo, non-toxic and showed activity and selectivity against Gram positive bacteria. Whilst such selectivity is an advantage, an extension of activity of such agents towards Gram negative organisms and eventually targeting cancer cells would be valuable. Since the biological properties of such minor groove bonders are related to the chemical feature, this aim could be achieved by modifying the structure of the tail group only. The MPhil project involved the synthesis of a small number of selected minor groove binders differing in their tail groups (Boc protected, OAc protected, guanidine, cyano alkene, nitro alkene) but bearing the same fluorescent head group ((E)-4-(3-methoxystyryl)benzyl). The yield of the coupling reaction between the head group and the pyrrole-pyrrole core linked with a protected tail group (Boc or OAc) was improved up to two- to five- fold, using propane phosphonic acid anhydride as a mild reagent. These MGBs were then evaluated for anti-bacterial and anti-cancer drug activity in screens available at the Strathclyde Institute of Pharmaceutical and Biological Sciences (SIPBS). They were tested against Gram negative E. coli, against Gram positive Staph. aureus and against the fibroblast hamster cell line V79, in order to evaluate respectively their anti-bacterial activity and their toxicity. The penetration of these synthesized molecules into bacteria and cells was observed under microscopy in order to assess the structural features that could lead to a potential anti-bacterial and/or anti-cancer molecule if nuclear permeation occurs. Almost all MGBs tested permeate into Gram positive bacteria, but not all of them showed an anti-bacterial activity. These results were consistent with earlier expe…
author: Bourdin, Claire
date published: 2011
date modified: 2026-07-24T04:50:01Z
provider: University of Strathclyde
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Strathclyde

PropertyValue
property ID: DOI
value: 10.48730/yqg8-2598