Conformationally constrained D,L‐alternating oligopeptides

Abstract

The possibility of selectively reducing the number of beta-helical structures theoretically possible for a D,L-alternating peptide by using a N-methyl group as conformational constraint is considered. Some 1H-nmr data regarding Boc(L-Nle-D-Nle)3-L-Nle-D-MeNle-L-Nle-D-Nle-L-Nle-OMe (I), its formyl analogue (II), and the pentadecapeptide Boc(D-Leu-L-Leu)5-D-MeLeu-(L-Leu-D-Leu)2-OMe (III) are presented. It is shown that these alternating stereocooligopeptides with a N-methyl group in the (n - 3) (I and II) or (n - 4) position (III) differ drastically in their behavior from the corresponding nonmethylated compounds. In chloroform, I and II form predominantly -- beta 7.2-helices and III forms almost exclusively -- beta 5.6 or -- beta 7.2-helices. The helices are in every case those having the maximum possible number of interchain H bonds.

Solution NMR structure of aD,L-alternating oligonorleucine as a model of ?-helix

“…There has been established a direct correlation between the participation of an NH group in a H bond and its δ NH for oligopeptides in nonpolar solvents 11. The δ NH > 7.0 ppm for those NH groups implied in H bond, whereas for those not involved in H‐bond δ NH the values are between 6.5 and 7.0 ppm.…”

“…Several D,L ‐alternating oligonorleucine have been synthesized for the characterization of these structures and to study the contribution of hydrophobic interaction of the linear side chains that stabilize one specific helical conformation. In attempts to achieve specific kinds of β‐helices by using the N‐methyl group as conformational constraint, a set of D,L ‐alternating oligonorleucines having a N‐methylated residue at the fourth‐last position of the chain10, 11 were synthesized and investigated.…”

Solution NMR structure of a D,L‐alternating oligonorleucine as a model of β‐helix

“…There has been established a direct correlation between the participation of an NH group in a H bond and its ␦ NH for oligopeptides in nonpolar solvents. 11 The ␦ NH Ͼ 7.0 ppm for those NH groups implied in H bond, whereas for those not involved in H-bond ␦ NH the values are between 6.5 and 7.0 ppm. From the Table I it can be observed that the residues with ␦ NH Ͼ 7.0 ppm are 3, 5, 6, 7, 8, 10, and 12, whereas those with ␦ NH between 6.5 and 7.0 ppm are 2, 4, and 11.…”

Double helix formation in α‐peptides: a theoretical study

“…the backbone torsion angles of every second amino acid agree. It was very interesting to see two alternating L , D ‐polypeptide strands forming double helices as an alternative to the single‐stranded helices (Figure 1b and c)8–19.…”