@article{bibcite_263,
  keywords = {Models, Molecular, Animals, Structure-Activity Relationship, Oligopeptides, Molecular Structure, Peptide Fragments, Magnetic Resonance Spectroscopy, Amyloid beta-Peptides, Protein Multimerization, Biological Products, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Drosophila melanogaster, Female, PC12 Cells, Protein Stability, Rats},
  author = {A. Frydman-Marom and M. Convertino and R. Pellarin and A. Lampel and R. Shaltiel-Karyo and D. Segal and A. Caflisch and D. E. Shalev and E. Gazit},
  title = {Structural basis for inhibiting β-amyloid oligomerization by a non-coded β-breaker-substituted endomorphin analogue},
  abstract = {<p>The distribution of endomorphins (EM) 1 and 2 in the human brain inversely correlates with cerebral neurodegeneration in Alzheimer{\textquoteright}s disease (AD), implying a protective role. These endogenous opioid peptides incorporate aromatic residues and a \&beta;-breaker motif, as seen in several optimized inhibitors of A\&beta; aggregation. The activity of native endomorphins was studied, as well as the rationally designed analogue Aib-1, which includes a remarkably efficient \&beta;-breaker, \&alpha;-aminoisobutyric acid (Aib). In vitro and GFP fusion protein assays showed that Aib-1 interacted with A\&beta; and markedly inhibited the formation of toxic oligomer and fibril growth. Moreover, Aib-1 prevented the toxicity of A\&beta; toward neuronal PC12 cells and markedly rectified reduced longevity of an AD fly model. Atomistic simulations and NMR-derived solution structures revealed that Aib-1 significantly reduced the propensity of A\&beta; to aggregate due to multimode interactions including aromatic, hydrophobic, and polar contacts. We suggest that hindering the self-assembly process by interfering with the aromatic core of amyloidogenic peptides may pave the way toward developing therapeutic agents to treat amyloid-associated diseases.</p>},
  year = {2011},
  journal = {ACS Chemical Biology},
  volume = {6},
  pages = {1265-1276},
  month = {2011 Nov 18},
  issn = {1554-8937},
  doi = {10.1021/cb200103h},
  language = {eng},
}