RHN Jn HacHJI 5 J 3 L V

Fig. 1.8 Examples of aliphatic oligomers, the conformations of which are defined by interactions between adjacent units.

The 3,5-linked polypyrrolin-4-one scaffold (Fig. 1.8a) allows for a wide variety of folding motifs. This outcome may be ascribed to the cooperative effect of: (i) the dihedral angles of the backbone that are locked by the pyrrolinone ring, (ii) restricted rotations due to gauche steric interactions between the side chains and the neighboring pyrrolinone rings, and (iii) C=O---H-N intramolecular H-bonds between adjacent pyrrolinone rings [102]. The 3,5-linked homochiral polypyrroli-none motif provides for an excellent b-sheet/b-strand peptidomimetic [111]. On the other hand, alternating d,l (heterochiral) polypyrrolinones preferentially adopt a b-turn [112]. Finally, studies of N-methylated bispyrrolinones indicate the possibility to obtain b-turn and helical structures [113].

The use of g-lactams such as (2S,4R)-4-amino-5-oxopyrrolidine-2-carboxylic acid as conformationally constrained dipeptide building blocks locks every other amide linkage in the cis conformation resulting in rigid peptide foldamers with an alternating cis-trans amide sequence (Fig. 1.8b). In the solid state, the trimer folds into a crescent shape. Unconstrained backbone f and c torsional angles are 100 G 15° and 138 G 13°, showing that the expected intramolecular hydrogen bonds between the amide NH and the lactam carbonyl and between the lactam NH and the amide carbonyl do not occur. In the solid, intermolecular hydrogen bonds apparently prevail over intramolecular hydrogen bonding [103].

Foldamers that contain the 4-carboxy-5-methyloxazolidin-2-one unit fold into well-defined b-bend ribbon spirals (Fig. 1.8c). Factors that influence folding in these strands include: (i) the rigid - CO - N(CH<) - CO - moiety, which favors a trans conformation, (ii) the formation of C=O---H-Ca hydrogen bonds, and (iii) the formation of alternate 1 ^ 4 intramolecular C=O---H-N hydrogen bonds

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