Synthesis, conformational analysis, and spectroscopic characterization of peptides based on Daf, the first rigid transition-metal receptor, cyclic C(alpha,alpha)-disubstituted glycine.
Three series of terminally protected model oligopeptides to the nonamer level, based on 9-amino-4,5-diazafluorene-9-carboxylic acid, the first rigid bipyridine-type C(alpha,alpha)-disubstituted glycine, and either Gly, L-Ala, or Aib residues were synthesized by solution methods and fully characterized. The molecular structures of two derivatives and one tripeptide were determined in the crystal state by x-ray diffraction. Moreover, the solution preferred conformations of these peptides were assessed by Fourier transform infrared absorption and (1)H-NMR techniques. A comparison with the known structural tendencies of the strictly related C(alpha,alpha)-disubstituted glycyl residues 1-aminocyclopentane-1-carboxylic acid and 9-aminofluorene-9-carboxylic acid is made, and the implications for the use of the 9-amino-4,5-diazafluorene-9-carboxylic acid residue in conformationally constrained analogs of bioactive peptides are briefly examined. A spectroscopic (uv absorption, fluorescence, CD) characterization of this novel heteroaromatic C(alpha,alpha)-disubstituted glycine is also reported. Finally, preliminary conformational data and membrane activity measurements are discussed for an analog of the lipopeptaibol antibiotic [L-Leu(11)-OMe] trichogin GA IV in which a 9-amino-4,5-diazafluorene-9-carboxylic acid residue was synthetically incorporated in position 1 (replacing the original Aib residue).
Peggion
Cristina
C
Biopolymer Research Center, CNR, Department of Organic Chemistry, University of Padova, Via Marzolo 1, 35131 Padua, Italy.
Crisma
Marco
M
Formaggio
Fernando
F
Toniolo
Claudio
C
Wright
Karen
K
Wakselman
Michel
M
Mazaleyrat
Jean-Paul
JP
D001372:Aza Compounds / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D005998:Glycine / Q000737:chemistry*; D007259:Infrared Rays; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D017550:Spectroscopy, Fourier Transform Infrared; D014466:Ultraviolet Rays; D014961:X-Ray Diffraction
C453700:9-amino-4,5-diazafluorene-9-carboxylic acid; D001372:Aza Compounds; D002264:Carboxylic Acids; D008670:Metals; D010455:Peptides; D005998:Glycine