Studies of repeating synthetic peptides designed to adopt a cross‐β conformation

Three polypeptides with the sequence poly(Gly‐Gln‐[Val‐Val] n ‐Asn‐Pro) have been synthesised with n = 0, 1 or 2. The polyoctapeptide sequence is designed as a model for cross‐β structures, in particular those described for the microcrystalline parts of certain feather keratins (Fraser & MacRae (1976) Proc. 16th Int. Ornithol. Congress, Canberra, 1974). The circular dichroism (CD) spectra of all three polypeptides in trifluoroethanol are similar to those of the corresponding monomeric tetra‐, hexa‐ and octapeptides, with double minima near 205 and 220 nm and maxima near 193 nm. Accordingly, these polypeptides are believed to adopt repeating type I(III) β‐bends stabilised by H‐bonds involving Asn side chains. The difference CD spectrum produced by subtracting the spectrum for poly(GlyGlnAsnPro) from that of poly(GlyGlnVal 4 AsnPro) is typical of that for a β‐sheet, suggesting that the Val residues adopt a β‐strand conformation. Aqueous solutions of the polyhexapeptide can be induced to take up similar CD spectra on heating, presumably due to induced hydrophobic interactions between the Val β‐strands. X‐ray diffraction patterns on unoriented films of the polypeptides add weight to the conclusion that the polyoctapeptide folds up into a cross‐β structure with an inter‐strand spacing of 4.6 Å, a strand length of 23 Å and an inter‐sheet distance of 9.4 Å.