ANTIPARALLEL BETA-SHEET CONFORMATION IN CYCLOPEPTIDES CONTAINING A PSEUDO-AMINO ACID WITH A BIPHENYL MOIETY

The biphenyl-containing pseudo-amino acids 2'-(aminomethyl)biphenyl-2- carboxylic acid (Abc; 1) and 2'-(aminomethyl)biphenyl-2-acetic acid (A ba; 2) are used as rigid spacers in the backbone of the cyclic peptide s cycle (-Abc-Ala-Phe-Gly-)(2) (5), cyclo(-Abc-Ala-Val-Gly-)(2) (6), c yclo(-Aba-Gly-Phe-Ala-)(2) (7), and cyclo(-Aba-Ala-Phe-Gly-)(2) (8). T hree different interconverting diastereoisomers are found in solutions of each of these cyclopeptides due to the atropisomerism of the biphe nyl units. NMR Techniques and molecular-dynamics calculations allow to conclude that the major diastereoisomer of 5 (and 6) in (D-6)DMSO ado pts a beta-sheet conformation. It is proposed that the pseudo-amino ac id 1 of (R)-chirality forms, with attached L-amino acids, a H-bonding pattern comparable to a beta-turn (see D in Fig. 4 and F).