Synthesis and structural investigations of N-alkylated β-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. It was found that variation of merely the alkyl chain induced a dramatic variation in aggregation motifs such as helical ribbons and tapes, ribbons progressing to closed tubes, twisted lamellar sheets and entangled/branched fibers.