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sullivjo

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About sullivjo

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  • Favorite Area of Science
    Medicinal Chemistry
  1. You are correct. I have no specific bacterial types in mind nor have i suggested controlled damage to dna as my knowledge of this topic is somewhat limited. I feel the ku complex is a good target for inhibition as it is very conserved among bacteria thus resistant mutants are unlikely to develope as the amino acid sequence seems to be very constrained. My strategy is very general and crude, i was simply spreading the idea in light of new multi-resistant bacteria.
  2. Thanks for the correction, for some reason I associated mitochondria with nanoparticles. I was simply suggesting mitochondria as an alternative to exosomes.
  3. The packing of drugs into mitochondria for administration and delivery to the site of action in vivo could be efficient as it could avoid immune response being an endogenous nanoparticle and be membrane permeable with improved drug lifetime. Attachment of mAbs to the outer membrane may direct it to the desired cells/site of action. This method may be also possible for gene therapy. Is this method feasible or at least a worthwhile topic of research?
  4. X-Rays cause the damage to both strands of DNA, if the Ku protein function is inhibitted, the DNA will be irreparably damaged which should trigger apoptosis.
  5. The Ku complex is essential for repair of double strand breaks in DNA following exposure to X-Rays. This complex differs in structure between eukaryotes and prokaryotes in which it forms a heterodimer and homodimer respectively. It is also smaller in prokaryotes. These structural differences could be exploited to design a selective inhibitor of the Ku complex in bacteria where subsequent exposure to X-Rays may cause irreparable damage to their DNA thus killing them. Could this be a feasible form of treatment or a worthwhile topic of research? Reference; Bacterial Nonhomologous End Joining Requires Teamwork, Lindsay A. Matthews and Lyle A. Simmons, J Bacteriol. 2014 Oct; 196(19): 33633365.
  6. Are there any organic molecules that display red phosphorescence in aqueous solution? Their conjugation with an antibody targetted to cancer cells may sufficiently expose the photosensitizing agents to red light deep within the body thus producing singlet oxygen for killing of the cells.
  7. The Ku complex is essential for DNA repair following double strand breaks following exposure to X-Rays. Potential inhibitors of this Ku complex could either block its interaction with the DNA backbone by binding as an anionic phosphate analogue or block formation of the required Ku70/Ku80 heterodimer for DNA repair. These inhibitors can be selectively targeted to cancer cells by conjugation to a macromolecule such as polyethylene glycol which should enter tumour cells via the EPR effect or monoclonal antibodies which bind biomarkers. Could selective inhibition of this Ku complex within malignant tumours with subsequent exposure to X-Rays be an effective method of shrinking tumours or at least be a potential topic of research? Reference; Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair, John R. Walker1,2, Richard A. Corpina & Jonathan Goldberg, Nature 412, 607-614 (9 August 2001)
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