Synthesis and structural investigations of N-alkylated beta-peptidosulfonamide-peptide hybrids of the amyloidogenic amylin(20-29) sequence: Implications of supramolecular folding for the design of peptide-based bionanomaterials.

The incorporation of a single beta-aminoethane sulfonyl amide moiety in a highly amyloidogenic peptide sequence resulted in a complete loss of amyloid fibril formation. Instead, supramolecular folding morphologies were observed. Subsequent chemoselective N-alkylation of the sulfonamide resulted in amphiphilic peptide-based hydrogelators.

Self-assembly of amylin(20-29) amide-bond derivatives into helical ribbons and peptide nanotubes rather than fibrils.

Uncontrolled aggregation of proteins or polypeptides can be detrimental for normal cellular processes in healthy organisms. Proteins or polypeptides that form these amyloid deposits differ in their primary sequence but share a common structural motif: the (anti)parallel beta sheet. A well-accepted approach for interfering with beta-sheet formation is the design of soluble beta-sheet peptides to disrupt the hydrogen-bonding network; this ultimately leads to the disassembly of the aggregates or fibrils.