Microwave-assisted click polymerization for the synthesis of Abeta(16-22) cyclic oligomers and their self-assembly into polymorphous aggregates.
We report on the design, synthesis, and structural analysis of cyclic oligomers with an amyloidogenic peptide sequence as the repeating unit to obtain novel self-assembling bionanomaterials. The peptide was derived from the Alzheimer Abeta(16-22) sequence since its strong tendency to form antiparallel beta-sheets ensured the formation of intermolecular hydrogen bridges on which the supramolecular assembly of the individual cyclic oligomers was based. The synthesis of the cyclic oligomers was performed via a microwave-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction of azido-Lys-Leu-Val-Phe-Phe-Ala-Glu-propargyl amide as the monomer. The formation of cyclic oligomers, up to pentamers (35 amino acid residues), was verified by MALDI-TOF analysis and the individual cyclic monomer and dimer could be isolated by HPLC. Gelation behavior and the self-assembly of the linear monomer and the cyclic monomer and dimer were studied by TEM, FTIR and CD. Significant differences were observed in the morphology of the supramolecular aggregates of these three peptides that could be explained by alterations of the hydrogen bond network.
Elgersma
Ronald C
RC
Division of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
van Dijk
Maarten
M
Dechesne
Annemarie C
AC
van Nostrum
Cornelus F
CF
Hennink
Wim E
WE
Rijkers
Dirk T S
DT
Liskamp
Rob M J
RM
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D032701:Biomimetics; D006860:Hydrogen Bonding; D008872:Microwaves; D008958:Models, Molecular; D043942:Nanotubes / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011108:Polymers; C417223:amyloid beta-protein (16-22)