Ab Initio Conformational Space Study of Model Compounds of O-Glycosides of Serine Diamide (original) (raw)
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Conformational studies on model dipeptides of Gly, L -Ala and their Cα-substituted analogs
International Journal of Peptide and Protein Research, 1995
As a part of the development of conformational guidelines for the design of metabolically altered peptidomimetics, we present conformational energy calculations on model dipeptide compounds with glycine (Gly), L-alanine (Ala), alpha-aminoisobutyric acid (Aib), L-tert-butylglycine (Tle), L-phenylglycine (Phg), (alpha, alpha)-diphenylglycine (D phi g), L-2-aminobutyric acid (Abu), 2-amino-2-ethylbutyric acid (Deg), L-2-amino-2-vinylacetic acid (Ava) and (alpha, alpha)-divinylglycine (Dvg). The energy calculations have been made using molecular mechanics methods with a force field derived from MM2. The salient features are expressed in terms of conformational energy plots, drawn as a function of the backbone torsion angles phi(Ci'-1-Ni-Ci alpha i-Ci') and psi(Ni-Ci alpha -C'-N(i+1)). The low-energy structures of these compounds are qualitatively consistent with the X-ray crystal structure analyses of peptides and peptidomimetics. They are also in agreement with the results of the solution-phase studies carried out by NMR and IR techniques. The results obtained have important implications in the design of conformationally restricted peptidomimetics.
The Journal of Physical Chemistry A, 2006
Ab initio molecular orbital computations were carried out at three levels of theory: RHF/3-21G, RHF/6-31G(d), and B3LYP/6-31G(d), on four model systems of the amino acid proline, HCO-Pro-NH 2 [I], HCO-Pro-NH-Me [II], MeCO-Pro-NH 2 [III], and MeCO-Pro-NH-Me [IV], representing a systematic variation in the protecting N-and C-terminal groups. Three previously located backbone conformations, γ L , L , and R L , were characterized together with two ring-puckered forms syn (gauche + ) g + ) or "DOWN" and anti (gauche -) g -) or "UP", as well as trans-trans, trans-cis, cis-trans, and cis-cis peptide bond isomers. The topologies of the conformational potential energy cross-sections (PECS) of the potential energy hypersurfaces (PEHS) for compounds [I]- [IV] were explored and analyzed in terms of potential energy curves (PEC), and HCO-Pro-NH 2 [I] was also analyzed in terms of potential energy surfaces (PESs). Thermodynamic functions were also calculated for HCO-Pro-NH 2 [I] at the CBS-4M and G3MP2 levels of theory. The study confirms that the use of the simplest model, compound [I] with P N ) P C ) H, along with the RHF/3-21G level of theory, is an acceptable practice for the analysis of peptide models because only minor differences in geometry and stability are observed.
The Journal of Physical Chemistry, 1995
An ab initio study of the conformational behavior of aand ,!%glycosidic linkages has been carried out on axial and equatorial 2-methoxytetrahydropyrans as models. The geometry of the conformers about the glycosidic C-0 bond was determined by gradient optimization at the SCF level using the 4-21G and 6-31G* basis sets and at the second-order Moller-Plesset level using the MP2/6-31G* basis set. The potential of rotation has been calculated using 4-21G, 6-31G*, 6-31+G*, MP2/6-31G*, and 6-31 l++G** basis sets. At all levels of theory, both axial and equatorial forms prefer the GT conformation around the C-0 glycosidic bond. Conformational changes in bond lengths and angles at the anomeric center also display significant variations with computational methods, but structural trends are in fair agreement with experiment. The correction for the effect of zero-point energy, thermal energy, and entropy on the axial-equatorial energy difference at the 6-31G* level is-0.63 kcal/mol. After these corrections to the energy difference calculated at the 6-31G* level, the axial form is favored by 0.84 kcaymol, in reasonable agreement with experimental values of AG = 0.7-0.9 kcaymol estimated for nonpolar solvents. Solvent effects reduce this energy difference; in the extreme case of water, a value of 0.24 kcal/mol was obtained. Complete torsional profiles have been obtained for rotation about the glycosidic C-0 bond in eleven solvents, and the calculated energy differences are in fair agreement with experimental data on 2-alkoxytetrahydropyrans in solutions. The MM3 (6 = 1.5) force field reproduces the 6-31G* a b initio energy difference reasonably well, but barrier heights are in poor agreement with the ab initio data. The calculated energies and geometries provide an essential set of data for the parametrization of the behavior of acetal fragments in molecular mechanical force fields for carbohydrates.
Journal of The American Chemical Society, 2008
The biological addition of oligosaccharide structures to asparagine residues of N-glycoproteins influences the properties and bioactivities of these macromolecules. The linkage region constituents, 2-acetamino-2-deoxy--D-glucopyranose monosaccharide (GlcNAc) and L-asparagine amino acid (Asn), are conserved in the N-glycoproteins of all eukaryotes. In order to gain information about the structure and dynamics of glycosylated proteins, two chloroacetamido sugars, Glc NAcNHCOCH 2Cl and Man NHCOCH 2Cl, have been synthesized, and their crystal structures have been solved. Structural comparison with a series of other models and analogs gives insight about the influence of the N-acetyl group at position C2 on the conformation of the glycan-peptide linkage at C1. Interestingly, this N-acetyl group also influences the packing and network of hydrogen bonds with involvement in weak hydrogen bonds C-H · · · X that are of biological importance. DFT ab initio calculations performed on a series of models and analogs also confirm that the GlcNAc derivatives present different preferred conformation about the N-CO-CH 2-X ( 2) torsion angle of the glycan-peptide linkage, when compared to other monosaccharide derivatives. The energy profiles that have been obtained will be useful for parametrization of molecular mechanics force-field. The conjunction of crystallographic and computational chemistry studies provides arguments for the structural effect of the N-acetyl group at C2 in establishing an extended conformation that presents the oligosaccharide away from the protein surface. Cummings, R.; Esko, J.; Freeze, H.; Hart, G.; Marth, J.
An ab initio exploratory study of the full conformational space of MeCO-l-threonine-NH-Me
Journal of Molecular Structure: THEOCHEM, 2003
Ab initio molecular computations were carried out on N-and C-protected L-threonine. Molecular geometry optimizations were conducted on the 81 possible minimum energy conformers of the molecule at the RHF/3-21G level of theory; 39 conformers were located, of which 34 were common with N-and C-protected serine. The relative stabilities of the various conformers have been analyzed in terms of backbone -backbone and backbone -sidechain hydrogen bonding interactions. The stabilization energies exerted by the sidechain of threonine on the backbone are presented as well. q
Chemical Physics, 2013
Amino acid conformational analysis is widely studied in the literature. However, information about the intramolecular interactions that govern their conformational preferences is scarce and it is commonly attributed to intramolecular hydrogen bond formation. The present paper utilizes calculations at the B3LYP/aug-cc-pVDZ theoretical level and QTAIM and NBO methods for glycine, sarcosine and N,N-dimethylglycine conformers to emphasize that arbitrary literature interpretations are equivocal. Also, our results show that the interplay between steric and hyperconjugative interactions rules glycine conformer energies/geometries and such results are confirmed by sarcosine and N,N-dimethylglycine conformational preferences.
J Mol Struc Theochem, 1997
An ab initio study of the conformational behavior of aglycon OC glycosidic bonds and rotameric distribution in O-methylated carbohydrates has been carried out on axial and equatorial 1,2-, 1,3- and 1,4-dimethoxytetrahydropyran as models. The geometry of the conformers about the C(aglycon)O(glycosidic) bond (Ψ-type) in 12 models was determined by gradient optimization at the SCF level using split valence 6-31G∗ basis sets. The potential of rotation has been calculated using 6-31G∗ and 631 + G∗ basis sets. At all levels of theory, both axial and equatorial forms prefer the GT or TG conformers around the CO glycosidic bond over the GG conformer. Exceptions are models of (1 → 2) linkages with the equatorial anomeric methoxyl group (E2A and E2E), where the TG conformer is not present. Calculated potential energy profiles show high flexibility within a 1.5 kcal mol−1 low energy region that is 180 ° wide. The glycosidic bond angle ClOiCi depends on the torsion angle Ψ and assumes values in the interval from 115 ° to 125 °.
Journal of Molecular Structure: THEOCHEM, 1997
An ab initio study of the conformational behavior of aglycon O-C glycosidic bonds and rotameric distribution in Omethylated carbohydrates has been carried out on axial and equatorial 1,2-, 1,3and 1 $dimethoxytetrahydropyran as models. The geometry of the conformers about the C(aglycon)-O(glycosidic) bond (q-type) in 12 models was determined by gradient optimization at the SCF level using split valence 6-3lG* basis sets. The potential of rotation has been calculated using 6-3 lG* and 63 I + G* basis sets. At all levels of theory, both axial and equatorial forms prefer the GT or TG conformers around the C-O glycosidic bond over the GG conformer. Exceptions are models of (I -2) linkages with the equatorial anomeric methoxyl group (E2A and E2E), where the TG conformer is not present. Calculated potential energy profiles show high flexibility within a 1.5 kcal mol-' low energy region that is 180" wide. The glycosidic bond angle C 1 -Oi-Ci depends on the torsion angle \k and assumes values in the interval from 115" to 125". 0 1997 Elsevier Science B.V.
Carbohydrate Research, 1982
Carbon-13 nuclear magnetic resonance data fcr mono-and di-O-a-and-B-Dgalactosylated dipeptides composed of Thr and Gly are presented_ The results conclusively show that peptide-bond formation does not affect the chemical shift: of the attached carbohydrate carbon atoms. In the case of the di-0-glycosylated threonylthreonine, no carbohydrate-carbohydrate interactions could be observed_ For some of the mono-0-glycosylated dipeptides, the attached glycosyl group appears to have a peculiar effect on the chemical shifts of some of the carbon resonances of the amino acids. Glycoproteins are proteins to which carbohydrates are covalently attachedle6; they are widely distributed throughout Nature, and are by far the predominant form of extra-cellu!ar proteins3. Glycoproteins are known to be involved in enzymic catalysis, ion transport, surface protection, lubrication, molecular recognition, cellcell adhesion, and a variety of other physiological functions'. For some glycoproteins, it has been postulated that the carbohydrates are necessary for maintainin, m the structure (conformation) and function of the molecule 7-1o_ The functional conformation of porcine ribonuclease B and glucoamylase from Aspergihs niger depends on oligosaccharide chains covalently bound to amino acids (such as Asn, Thr, and Ser) throughout the molecule'~'l-. However, in the human-erythrocyte membrane-glycoprotein, glycophorin A, the display of the MN determinants and some general receptor functions appear to be associated with the carbohydrate residues which are located only near the N-terminal region12. In this particular case, the points of glycosylation are not distributed randomly (and far