Filomena Rossi

[Aib5,6-d-Ala8]-Cyclolinopeptide A, Grown from a Benzene/Acetonitrile Mixture

cyclo-(Prolyl-prolyl-phenylalanyl-phenylalanyl- alpha-aminoisobutyryl-alpha-aminoisobutyryl-isoleucyl-D-alan yl-valyl) ([Aib5,6-D-Ala8]-cyclolinopeptide A), grown from benzene/acetonitrile mixture, crystallizes with one acetonitrile and two water molecules. The molecular structure is almost identical to that obtained from methanol/water. The dimension of the solvent channels found in these structures is reduced in the present one, but the intramolecular hydrogen-bond pattern is preserved. The Pro1-Pro2 peptide unit is cis (omega = 8 degrees); all others are trans.

Synthesis and conformation of dipeptide taste ligands containinghomo-β-amino acid residues

The synthesis and conformational properties of a series of dipeptide taste ligands, differing from the commercial sweetener aspartame by the presence of a methylene group between the Cα and the C′ carbon atoms (as in homo-β-residues) in either the L-Asp or the L-Phe residues, are described. Homo-β-residues such as homo-β-aspartic acid, homo-β-phenylglycine and homo-β-phenylalanine, obtained by homologation of the corresponding proteinogenic α-amino acids, have been used in the solution peptide synthesis of the following aspartame analogues in protected and unprotected forms: NH2-homo-β-(L or D)-Asp-L-Phe-OMe, NH2-L-Asp-homo-β-L-Phg-OMe and NH2-L-Asp-homo-β-L-Phe-OMe. Lengthening of the peptide skeleton at the L-Asp site results in a drastic loss of sweetness with the production of tasteless compounds; on the other hand, lengthening of the skeleton at the C-terminal L-Phe site partially mantains the sweet taste in both NH2-L-Asp-homo-β-L-Phe-OMe and NH2-L-Asp-homo-β-L-Phg-OMe.The solution conformation of the synthesized dipeptide taste ligands was investigated by NMR and circular dichroism techniques. The analysis of NMR data combined with restrained molecular dynamics calculations shows that all peptides are fairly flexible and they do not assume a preferred conformation in DMSO and methanol. The peptides containing homo-β-L-Phe and homo-β-L-Phg do adopt a discrete number of conformations among which mainly extended and ‘L-shaped’ conformation are represented. The circular dichroism spectra are consistent with the NMR results, indicating a significant flexibility for these compounds. Copyright

Effect of lengthening of peptide backbone by insertion of chiral ?-homo amino acid residues: Conformational behavior of linear peptides containing alternatingL-leucine and ?-homoL-leucine residues

The synthesis and the solution behavior of the linear peptides containing a beta-homo (beta-H) leucine residue-Boc-Leu-beta-HLeu-Leu-OMe, Boc-beta-HLeu-Leu-beta-HLeu-Leu-OMe, and Boc-Leu-beta-HLeu-Leu-beta-HLeu-Leu-OMe-as well as the solid structure of the tripeptide, are reported. The conformational behavior of the peptides was investigated in solution by two-dimensional nmr. Our data support the existence in solution with different families of conformers in rapid interchange. The crystals of the tripeptide are orthorhombic, space group P2(1)2(1)2, with a = 15.829(1) A, b = 29.659(1) A, c = 6.563(1) A, and Z = 4. The structure has been solved by direct methods and refined to final R1 and wR2 indexes of 0.0530 and 0.1436 for 2420 reflections with I > 2sigma(I). In the solid state, the tripeptide does not present intramolecular H bonds, and the peptide backbone of the two leucine residues adopts a quasi-extended conformation. For the beta-HLeu residue, the backbone conformation is specified by the torsion angles straight phi(2) = -120.9(4) degrees, mu(2) = 56.7(4) degrees, psi(3) = -133.2(4) degrees. The side chains of the three residues assume the same conformation (g(-), g(-), trans), and all peptide bonds, except the urethane group at the N-terminus, are in the trans conformation. Preliminary conformational energy calculations carried out on the Ac-NH-beta-HAla-NHMe underline that the conformations with mu angle equal to 180 degrees and 60 degrees assume lower energy with respect to the others. In addition, we found a larger conformational freedom for the psi angle with respect to the straight phi angle.