Research ArticlePrion Disease

Structure-based drug design identifies polythiophenes as antiprion compounds

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Science Translational Medicine  05 Aug 2015:
Vol. 7, Issue 299, pp. 299ra123
DOI: 10.1126/scitranslmed.aab1923

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Putting prions in their place

In a mouse model of prion disease, Herrmann et al. evaluated the therapeutic efficacy of luminescent conjugated polythiophenes (LCPs), which are molecules with a high affinity for ordered protein aggregates. Intracerebral administration of LCPs into prion-infected mice using osmotic pumps increased survival. Solid-state nuclear magnetic resonance and in silico binding studies of LCPs to simplified model fibrils allowed the authors to define structural rules, which they then used for the design of LCPs with superior prophylactic and therapeutic potency. The new work demonstrates the feasibility of rational drug design for developing therapeutics to treat prion diseases.

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