ON INTRAHELICAL HYDROGEN-BONDING AND STABILITY OF BETA-HELICES - THE BEHAVIOR OF SOME D,L-ALTERNATING OLIGOLEUCINES WITH AN N-METHYLATED RESIDUE

An N-methylated residue at the n - 3 position of the chain was used to reduce the maximum number of H-bonds realizable by some D,L-alternating oligopeptides in beta4.4-, up upbeta5.6- and up downbeta5.6-helices and thus increase for the oligopeptides, the relative stability of larger beta-helices. With D,L-alternating oligoleucines of the series Boc-Leu(n)-OMe, however, this approach did not produce the helices expected. Although up downbeta7.2-helices with only one free NH per strand would theoretically be possible, the N-methylated oligoleucines formed instead flawed beta4.4-helices having three free NH's in CHCl3 as well as in other solvents of low polarity. These observations confirm that the stability of beta-helices does not depend only on the number of intra- or interstrand H-bonds, and corroborate the idea that beta-helices with large cavities are inherently unstable.