Cyclopropane Amino Acids That Mimic Two χ1-Conformations of Phenylalanine

✍ Scribed by Destardi Moye-Sherman; Song Jin; Shiming Li; Michael B. Welch; Joe Reibenspies; Kevin Burgess

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 273 KB
• Volume: 5
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/(sici)1521-3765(19990903)5:9<2730::aid-chem2730>3.0.co;2-x

✦ Synopsis

A highly constrained analogue of phenylalanine was prepared in optically pure form. This disubstituted cyclopropane amino acid, DiFi, realises two c 1 values of the phenylalanine side chain. Unlike monosubstituted analogues, amino acids of this type impart very specific perturbations at the N and C termini simultaneously. Model studies were performed to elucidate the intrinsic conformational biases of this amino acid and its isomeric analogue FiFi. These derivatives were incorporated into a simple model to determine the propensity of these compounds for gturn (or inverse g-turn) conformations. Three other phenylalanine derivatives (1--3) were also prepared for comparison purposes. Structural biases were assessed by CD, IR, and NMR spectrsocopy, X-ray crystal structure analysis, and molecular simulations. CD and IR spectra indicated that the two disubsti-tuted derivatives DiFi and FiFi contain secondary structural elements that appear to be absent in the other analogues. Molecular simulation protocols that involved grid-search routines were used to explore the conformational space accessible to derivatives 1 ± 5. These indicated that the FiFi derivative 5 was the most rigid of the analogues and that both the inverse g-turn and the left-handed ahelix appear to be accessible conformations.