Improved δ-valerolactam templates for the assembly of Aβ-miniamyloids by boronic ester formation.
The 6,7,8,8a-cis (all-cis) substituted δ-valerolactams of type 10, 11 and 12 are high-affinity diols for boronic ester formation, superior to the corresponding 6,7-trans analogues 1, 3 and 4. X-ray and NMR structure analysis have identified the differences of the six-membered ring conformations which cause the improved esterification properties of the all-cis stereoisomers. The homooligomeric all-cisδ-valerolactams 46-48 are used as polyol templates for the self-assembly of peptidic oligomers 49-52 by dynamic covalent chemistry. The templates have a diol spacing of approximately 5 Å, suitable for the assembly of branched peptides from the quantitative reaction between the peptide of interest, 2-formylphenylboronic acid and the respective template. According to this strategy, the tetrameric Aβ-miniamyloid 52 formed spontaneously from nine individual molecules in a three-component system. A detailed NMR analysis based on the complete sequential assignment of the trimeric Aβ(32-40)-miniamyloid 51 identified its three-dimensional structure in solution.
Institute of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany. geyer@staff.uni-marburg.de.
André
A
Wuttke
Sebastian Nils
SN
Fischer
Annika
A
Nebel
Michael
M
Marsch
Armin
A
Geyer
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D008958:Models, Molecular; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D016229:Amyloid beta-Peptides; D001897:Boronic Acids; D004952:Esters; D007769:Lactams; C511520:valerolactam