Synthesis, conformational study, and spectroscopic characterization of the cyclic C alpha, alpha-disubstituted glycine 9-amino-9-fluorenecarboxylic acid.
A series of terminally blocked peptides (to the pentamer level) from L-Ala and the cyclic C alpha, alpha-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 C alpha, alpha-disubstituted Gly residues Ac5c and D phi g 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 C alpha, alpha-disubstituted Gly residue is also reported.
Savrda
J
J
SIRCOB, Bât, Lavoisier, University of Versailles, France.
Mazaleyrat
J P
JP
Wakselman
M
M
Formaggio
F
F
Crisma
M
M
Toniolo
C
C
D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D003460:Crystallization; D005449:Fluorenes / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
C119175:9-amino-9-fluorenecarboxylic acid; D000596:Amino Acids; D005449:Fluorenes; D010455:Peptides; D005998:Glycine