Chiral discrimination in biomimetic systems: Phenylalanine (original) (raw)
Related papers
Crystal-state conformation of C?,?-dialkylated peptides containing chiral ?-homo-residues
Journal of Peptide Science, 2001
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 i-homo-amino acids, the synthesis and conformational characterization by X-ray diffraction analysis of peptides containing conformationally constrained C h,h -dialkylated amino acid residues, such as h-aminoisobutyric acid or 1-aminocyclohexane-1-carboxylic acid and a single i-homoamino acid, differently displaced along the peptide sequence have been carried out. The peptides investigated are: Boc-iHLeu-(Ac 6 c) 2 -OMe, Boc-Ac 6 c-iHLeu-(Ac 6 c) 2 -OMe and Boc-iHVal-(Aib) 5 -OtBu, together with the C-protected i-homo-residue HCl·H-iHVal-OMe. The results indicate that the insertion of a iH-residue at position 1 or 2 of peptides containing strong helix-inducing, bulky C h,h -disubstituted amino acid residues does not induce any specific conformational preferences. In the crystal state, most of the NH groups of i-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 C h,h -disubstituted amino acid residues. However, by repeating the structural motifs observed in the molecules investigated, a i-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 iH-residues, with the v torsion angle equal to −60°, are very unlikely.
Conformational analysis of the simplest chiral pseudo-peptide and selected derivatives
Journal of Molecular Structure: THEOCHEM, 2000
Conformational properties of three model pseudo-peptides were investigated by semi-empirical and ab initio MO methods. The three simplest model pseudo-peptides included the protonated form of N-formyl pseudo-alanineamid HCONH-CHMe-CH 2 NH 3 ϩ , N-formyl pseudo-alanine itself HCONH-CHMe-CH 2 NH 2 , as well as the formylated N-formyl pseudo-alanine (i.e. propylene-di(N-formylamine)) HCONH-CHMe-CH 2 NHCOH. It was shown that geometries of the pseudo-peptides in their global minima were determined by H-bonds. From the computated results, it follows that in general pseudo-peptides can mimic the backbone of the parent peptides. These computational results are in full agreement with previously reported experimental data. N-formyl pseudo-alanine was shown to be more flexible, than the parent peptide. ᭧
The Journal of Organic Chemistry, 2009
The intrinsic conformational preferences of the restricted phenylalanine analogue generated by including the α and β carbon atoms into a cyclohexane ring (1-amino-2phenylcyclohexanecarboxylic acid, c 6 Phe) have been determined using quantum mechanical calculations. Specifically, the conformational profile of the N-acetyl-N'-methylamide derivative of the c 6 Phe stereoisomers exhibiting either a cis or a trans relative orientation between the amino and phenyl substituents has been analyzed in different environments (gas phase, chloroform and aqueous solutions). Calculations were performed using B3LYP, MP2 and HF methods combined with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and a self-consistent reaction-field (SCRF) method was applied to analyze the influence of the solvent. The amino acids investigated can be viewed as constrained phenylalanine analogues with a rigidly oriented aromatic side chain that may interact with the peptide backbone not only sterically but also electronically through the aromatic π orbitals. Their conformational propensities have been found to be strongly influenced by the specific orientation of the aromatic substituent in each stereoisomer and the conformation adopted by the cyclohexane ring, as well as by the environment.
Journal of Molecular Structure: THEOCHEM, 1996
In a study of cross sections of the E -flx1,x2) side-chain conformational potential energy surface of the yL or CT? backbone conformation of For-L-Phe-NH*, it was found that there are three conformations (g + , a and g -) due to rotation about the Ca UC@ bond. It should be emphasised that the yL backbone conformation is conserved during rotation ahout x1. However, there is only one unique conformation along the rotation about the C? u Ph bond. The -CHr-Ph group showed greater stabihsation, with respect to hydrogen (Gly), than the -CHa (Ala) or -CHa-OH (Ser) substituents. The hydrogen-bonded C=O (amide 1) vibrational frequency is split into two bands due to the coupling of the C=O stretching and -NH2 scissoring modes of motion. The other carbonyl, not involved in hydrogen bonding, has a characteristic single IR band with a relatively high frequency. The orientation of the -Ph group has no appreciable effect on these vibrational frequencies.
Molecular quantum similarity of enantiomers of amino acids: a case study
Journal of Molecular Structure: THEOCHEM, 2005
In this paper, methodological in nature, molecular quantum similarity is evaluated for enantiomers in the case of molecules showing conformational flexibility, proposing the use of a Boltzmann weighted similarity index. As a case study, the conformers of the enantiomers of the amino acids Alanine and Serine were examined. The second aim is, next to studying global indices, the evaluation of local similarity using our earlier proposed local similarity index based on the Hirshfeld partitioning, in order to further quantify the consequences of Mezey's Holographic Electron Density Theorem in chiral systems.
2006
Hydrogen bond is one of the most important interactions in bio-molecular stability and recognition. Amino groups of nucleotides or amino acid residues act as important hydrogen bond donors in such interactions. The posi tions of the hydrogen atoms, which determine the directionality of the hydrogen bonds, are generally not available in the PDB entries. Although, such positions are reported in a few crystal structures, analysis of their geometry indicates that in most of them the positions are not thoroughly refined. The pyramidal nature of a few well-refined amino groups, however, indicates that a strong correlation exists between the non-planarity of the amide and the peptide torsion angles. The pyramidal nature of the amino groups might arise due to effect of lone pair electrons at the central nitrogen atoms, which do not take part in extended conjugation. In order to establish the above hypothesis, we have also studied a few amino group containing model systems by ab initio quantum chemical methods, which donate one of their lone pair electrons from nitrogen atoms during photo-induced electron transfer processes. The amino group of the excited state complex, geometry optimized by MCSCF/6-31 G** basis set, is found to have twisted planar geometry and the pyramidal nature is completely lost. This fUlther supports the effect of lone-pair electrons in the vicinity of a conjugated system in amino group non-planarity.
Journal of Molecular Structure: THEOCHEM, 2009
Structures of L-phenylalanine (phe) conformers were subjected to geometry optimization. Conformers of phe were optimized at the B3LYP and MP2 levels using the Gaussian 03 package. The relative energies, free energies and dipole moments of these conformers were subsequently calculated. The aggregation process of phe molecule has been also studied with B3LYP calculations using 6-31G Ã basis set. We suggest the possible mechanism of phenylalanine dimer formation. The interaction between two identical molecules of the amino acid involves hydrogen bonding AC@OÁ Á ÁHOOCA, forming cyclic dimers. Before dimer formation conformational changes (trans/cis isomerization) should occur. The trans form is energetically more stable than the cis one, but through an entropy-effect of association, the cis form can be dominating as it results in two hydrogen bonds. The conformational barrier height of cis/trans isomerization was calculated. The results are a continuation of our experimental studies on phenylalanine amino acid.