Crystal-state conformation of Calpha,alpha-dialkylated peptides containing chiral beta-homo-residues.
Secondary structure formation and stability are essential features in the knowledge of complex folding topology of biomolecules. To better understand the relationships between preferred conformations and functional properties of beta-homo-amino acids, the synthesis and conformational characterization by X-ray diffraction analysis of peptides containing conformationally constrained Calpha,alpha-dialkylated amino acid residues, such as alpha-aminoisobutyric acid or 1-aminocyclohexane-1-carboxylic acid and a single beta-homoamino acid, differently displaced along the peptide sequence have been carried out. The peptides investigated are: Boc-betaHLeu-(Ac6c)2-OMe, Boc-Ac6c-betaHLeu-(Ac6c)2-OMe and Boc-betaHVal-(Aib)5-OtBu, together with the C-protected beta-homo-residue HCl.H-betaHVal-OMe. The results indicate that the insertion of a betaH-residue at position 1 or 2 of peptides containing strong helix-inducing, bulky Calpha,alpha-disubstituted amino acid residues does not induce any specific conformational preferences. In the crystal state, most of the NH groups of beta-homo residues of tri- and tetrapeptides are not involved in intramolecular hydrogen bonds, thus failing to achieve helical structures similar to those of peptides exclusively constituted of Calpha,alpha-disubstituted amino acid residues. However, by repeating the structural motifs observed in the molecules investigated, a beta-pleated sheet secondary structure, and a new helical structure, named (14/15)-helix, were generated, corresponding to calculated minimum-energy conformations. Our findings, as well as literature data, strongly indicate that conformations of betaH-residues, with the micro torsion angle equal to -60 degrees, are very unlikely.
Centro di Studio di Biocristallografia, C.N.R. and Dipartimento di Chimica, Università degli Studi di Napoli Federico II, Italy.
A
A
Romanelli
I
I
Garella
V
V
Menchise
R
R
Iacovino
M
M
Saviano
D
D
Montesarchio
C
C
Didierjean
P
P
Di Lello
F
F
Rossi
E
E
Benedetti
D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D000598:Amino Acids, Cyclic / Q000737:chemistry; D000621:Aminoisobutyric Acids / Q000737:chemistry; D018360:Crystallography, X-Ray; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010452:Peptide Biosynthesis; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids; D003509:Cyclohexanecarboxylic Acids; D010455:Peptides; C100049:2-aminoisobutyric acid; C014966:1-aminocyclohexanecarboxylic acid