Accurate reproduction of the mechanism of peptide folding in solution and conformational preferences as a function of amino acid sequence is possible with atomic level dynamics simulations. For example, the simulations correctly predict a left‐handed 31‐helical fold for the β‐heptapeptide 1 (the molecular model is shown in the picture) and a right‐handed helical fold for the β‐hexapeptide 2, as was confirmed by NMR spectroscopy.

Dedicated to Professor Teruaki Mukaiyuma, a dear friend and revered colleague on the occasion of his 70th birthday(1 3. VIII. 96)Structural prerequisites for the stability of the 3, helix of p-peptides can be defined from inspection of models (Figs. 1 and 2 ) : lateral non-Hi-substituents in 2-and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of hepta- (1) and of the p-heptapeptide H-P-HVal-P-HAla-p-HLeu-(S,S)-~-HAla(a Me)-p-HVal-p-HAla-p-HLeu-OH (22), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such 8-peptides (previously discovered in pyridine solution) (Fig. 3 and Tables 1-5). The CD spectra of helicalp-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)-or ~-a-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 1 S 2 2 and 25 (including partially and fully deprotected forms) (Figs. 4 4 ) . The results fully confirm predicted structural effects: incorporation of a single 'wrong' residue ((R)-P-HAla, p-HAib, (R,S)-B-HAla(aMe), or N-Me-P-HAla) in the central positioh of thep-heptapeptide derivatives A (see 17, 18,20, or 21, resp.) causes the CD minimum to disappear. Also, the P-heptadepsipetide 25 (missing H-bond) and the /I-heptapeptide analogs with a single a-amino-acid moiety in the middle (13 and 14) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoicacid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H20).

No abstract

Enantiomerically pure a-amino-acid derivatives with the side chains of A h , Val, and Leu in the 2-or 3-position (8'-and P3-amino acids, resp.), as well as with substituents in both the 2-and 3-positions (Pz.3-amino acids, of like-configuration) have been prepared (compounds 8-17) and incorporated (by stepwise synthesis and fragment coupling, intermediates 24-34) into P-hexa-, P-hepta-, and j-dodecapeptides (1 -17). The new and some of the previously prepared P-peptides (35-39) showed NHiND exchange rates (in MeOH at room temperature) with T~,~ values of up to 60 days, unrivalled by short chain a-peptides. All P-peptides 1-7 were designed to be able to attain the previously described 3,-helical structure (Figs. I and 2). C D Measurements (Fig. 4), indicating a new secondary structure of certain P-peptides constructed of P'-and p3-arnino acids, were confirmed by detailed NMR solution-structure analyses: a P*-heptapeptide (2c) and a Pz.3-hexapeptide (7c) have the 3,-helical structure (Figs. 6 and 7), while to a P2/P3-hexapeptide (4) with alternating substitution pattern H-(P2-Xaa-P3-Xaa),-OH a novel, unusual helical structure (in (DJpyridine, Fig. 8; and in CD30H, Figs. 9 and f0) was assigned, with a central ten-membered and two terminal twelve-membered H-bonded rings, and with C=O and N-H bonds pointing alternatively up and down along the axis of the helix (Fig. 11). Thus, for the first time, two types of fi-peptide turns have been identified in solution. Hydrophobic interactions ofand hindrance to solvent accessibility by the aliphatic side chains are discussed as possible factors influencing the relative stability of the two types of helices.

regeneration were carried out as described.I7. Developing shoots were selected on 100 pgmL-' kanamycin.Fifteen kanamycin resistant plants were tested for cyanamide hydratase a~tivity!~] Enzyme activity was found in all plants, the level of expression ranging from 0.03 to 0.79 units per mg protein in the cell extract. The highest value corresponds to about a fifth of the specific activity measured in induced Myrothecium verrucaria extracts. Although the specific activity was highest in the roots, the total enzyme activity per gram fresh weight was distinctly higher in the leaves than in the other plant organs (Table 1). No activity was found in plants transgenic for cah-.