Racionální návrh konjugátů bis-akridinu s peptidy vážícími se k dsDNA

From the prepared library of bis-9-aminoacridine peptide conjugates, one compound exerting two orders of magnitude higher binding constant than that of 9-aminoacridine was identified

Nukleofilní substituce na akridinu - možný viník za interakci akridinu s prionovým proteinem

Covalent modification of lysine residue side chains in the hydrophobic core of prion protein aggregates could explain the discrepancy between the ability of the acridine drug quinacrine to reduce efficiently the incidence of prion protein in cell culture and its weak prion binding affinity

May bis-intercalator-peptides influence prion aggregation?

The synthesis of peptide libraries functionalized with 9-aminoacridines (Acr-NH2) was described as well as an assay based on precipitation of amyloidogenic dye from buffer solution HV monitoring of positional-scanning combinatorial libraries

Synthetic scan of C-domain from prion proteins

Prions are suspected as culprits of several neuropathogenic diseases. A combination of chemical and recombinant syntheses is a powerful tool for studying prion role in pathogenesis of neurodegenerative diseases. Due to the presence of “difficult” sequences in the prion protein molecule, chemical ligation procedure using peptide thioesters as key building blocks is a method of choice. Therefore, a synthetic scan of peptides constituting the mouse prion protein (MoPrP) C-domain 93-231 was carried out. The synthesis on chlorotritylchloride resin was the most promising for most peptides. Only the octadecapeptide MoPrP195-212 could not be synthesized by automated peptide synthesis even using the β-sheet breaking dipeptides. This difficulty was overcome by manual peptide synthesis with careful monitoring of coupling and Fmoc removal