The present work describes three novel nonpolar host peptide sequences that provide a ready assessment of the 3 10 -and a-helix compatibilities of natural and unnatural amino acids at different positions of small-to medium-size peptides. The unpolar peptides containing Ala, Aib, and a C-terminal p-iodoanilide group were designed in such a way that the peptides could be rapidly assembled in a modular fashion, were highly soluble in solvent mixtures of triflouroethanol and H 2 O for CD-and two-dimensional (2D) nmr spectroscopic analyses, and showed excellent crystallinity suited for x-ray structure analysis. To validate our approach we synthesized 9-mer peptides 79a-96 (Table ), 12-mer peptides 99-110c (Table ), and 10mer peptides 120a-125d and 129-133 (Table VI and Scheme 8) incorporating a series of optically pure cyclic and open-chain (R)-and (S)-a,a-disubstituted glycines 1-10 (Figure ). These amino acids are known to significantly modulate the conformations of small peptides.
Based on x-ray structures of 9-mers 79a, 80, and 87 (Figures ), 10-mers 124c, 131, and 132 (Figures 9-12), and 12-mer peptide 102b (Figure ), CD spectra of all peptides recorded in acidic, neutral, and basic media and detailed 2D-nmr analyses of 9-mer peptide 86 and 12-mer 102b, several interesting conformational observations were made. Especially interesting results were obtained using the convex constraint CD analysis proposed by Fasman on 9-mer peptides 79a-d, 80, 81, 86, and 87, which allowed us to determine the relative content of 3 10 -and a-helical conformations. These results were fully supported by the corresponding x-ray and 2D-nmr analyses. As a striking example we found that the (S)-and (R)-* Dedicated to Prof.