a foldamer-dendrimer conjugate neutralizes synaptotoxic β-amyloid oligomers一个foldamer-dendrimer共轭中和synaptotoxicβ-amyloid寡聚物.pdfVIP

A Foldamer-Dendrimer Conjugate Neutralizes Synaptotoxic b-Amyloid Oligomers ´ ¨ ¨ 1 ´ ´ 2 ´ ´ 1 3 ´ ´ 1 ´ 2 Lıvia Fulop , Istvan M. Mandity , Gabor Juhasz , Viktor Szegedi , Anasztazia Hetenyi , Edit Weber , ´ 1 ´ 1 ´ 4 ´ ´ 4 ´ 2 Zsolt Bozso , Dora Simon , Maria Benko˝ , Zoltan Kiraly , Tamas A. Martinek * ´ 1 Department of Medical Chemistry, University of Szeged, Szeged, Hungary, 2 Institute of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary, 3 Bay Zoltan Foundation for Applied Research – BAYGEN, Szeged, Hungary, 4 Department of Physical Chemistry and Materials Science, University of Szeged, Szeged, Hungary Abstract Background and Aims: Unnatural self-organizing biomimetic polymers (foldamers) emerged as promising materials for biomolecule recognition and inhibition. Our goal was to construct multivalent foldamer-dendrimer conjugates which wrap the synaptotoxic b-amyloid (Ab) oligomers with high affinity through their helical foldamer tentacles. Oligomeric Ab species play pivotal role in Alzheimer’s disease, therefore recognition and direct inhibition of this undruggable target is a great current challenge. Methods and Results: Short helical b-peptide foldamers with designed secondary structures and side chain chemistry patterns were applied as potential recognition segments and their binding to the target was tested with NMR methods (saturation transfer difference and transferred-nuclear Overhauser effec