Mutual interactions of basic peptides with nucleic and fatty acids – amyloid nucleation, membrane disruption, and hybridisation

Doctoral thesis English OPEN
Braun, Sebastian
  • Subject: QD | QH301

Anions including nucleic acids and lipids have been found to promote amyloid formation in diseases including neurodegenerative conditions such as Alzheimer’s and Creutzfeldt-Jakob disease. However, the direct effects of these close charge-based interactions are not well understood. It is unclear what effect amyloidogenic peptides would have on nucleic acid integrity. Similarly, the direct effects of amyloidogenic polypeptides on liposomes are not well understood. Here I have used a simplified system of short basic peptides with alternating hydrophobic and hydrophilic amino acid residues to study their interactions with polyanionic nucleic acids and fatty acid liposomes. Employing biophysical techniques including X-ray fibre diffraction, circular dichroism spectroscopy and electron microscopy I showed that the polymerized charges of nucleic acids and pseudo-polymerised charges of lipid membranes concentrated and enhanced the formation of amyloid from short basic peptides, many of which would not otherwise form fibres under the conditions explored. In turn, the same peptides bound nucleic acids and promoted their hybridisation at concentrations below their solution Kd, as shown by time-resolved FRET studies. The mutual interactions between peptides and nucleic acids lead to the formation of amyloid nucleic acid (ANA) fibres, which in addition to their importance in disease might have a potential in nano-engineering of biomaterials.
  • References (1)

    9.4.   Instrument  Response  Function  of  the  FRET  setup. ....................................................... x liv   9.5.   Additional  STVIIE  +  Oligo  E  Time  Courses. ........................................................................ x lv   9.6.   Overlay  Comparisons  of  Fibre  Diffraction  Patterns . ..................................................... x lvi   9.7.   Fatty  acid  spectra . .......................................................................................................................... l iii   9.8.   TVQFHMH  CD  Spectra. ................................................................................................................. l iv   9.9.   Hypothesis:  The  Amyloid-­‐Nucleic  Acid  (ANA)  World    as  Transition  from  the   RNA  World . ......................................................................................................................................................  lv  

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