Synthesis, conformational study, and spectroscopic characterization of the cyclic Cα,α-disubstituted glycine 9-amino-9-fluorenecarboxylic acid

Abstract

A series of terminally blocked peptides (to the pentamer level) from l-Ala and the cyclic Cα,α-disubstituted Gly residue Afc and one Gly/Afc dipeptide have been synthesized by solution method and fully characterized. The molecular structure of the amino acid derivative Boc-Afc-OMe and the dipeptide Boc-Afc-Gly-OMe were determined in the crystal state by X-ray diffraction. In addition, the preferred conformation of all of the model peptides was assessed in deuterochloroform solution by FT-IR absorption and 1H-NMR. The experimental data favour the conclusion that the Afc residue tends to adopt either the fully-extended (C5) or a folded/helical structure. In particular, the former conformation is highly populated in solution and is also that found in the crystal state in the two compounds investigated. A comparison with the structural propensities of the strictly related Cα,α-disubstituted Gly residues Ac5c and Dϕg is made and the implications for the use of the Afc residue in conformationally constrained analogues of bioactive peptides are briefly examined. A spectroscopic (UV absorption, fluorescence, CD) characterization of this novel aromatic Cα,α-disubstituted Gly residue is also reported. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.