Preferred conformation of peptides rich in Ac8c, a medium-ring alicyclic C (alpha,alpha)-disubstituted glycine.
A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C (alpha,alpha)-disubstituted glycine 1-aminocyclooctane-1-carboxylic acid (Ac8c), and two Ala/Ac8c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 1H-NMR. The molecular structures of the amino acid derivative Z-Ac8c-OH, the dipeptide pBrBz-(Ac8c)2-OH and the tripeptide pBrBz-(Ac8c)3-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Ac8c residue is an effective beta-turn and helix former. A comparison is also made with the conformational preferences of alpha-aminoisobutyric acid, the prototype of C (alpha,alpha)-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc with n = 3, 5-7) investigated so far. The implications for the use of the Ac8c residue in peptide conformational design are considered.
Moretto
V
V
Department of Organic Chemistry, University of Padova, Italy.
Formaggio
F
F
Crisma
M
M
Bonora
G M
GM
Toniolo
C
C
Benedetti
E
E
Santini
A
A
Saviano
M
M
Di Blasio
B
B
Pedone
C
C
D000596:Amino Acids / Q000737:chemistry*; D000598:Amino Acids, Cyclic; D005998:Glycine / Q000031:analogs & derivatives*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D010455:Peptides; C014967:1-aminocyclooctanecarboxylic acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine