Density functional study of infinite polyserine chains

Two different helical conformations (alpha and 3-10 helices) of polyserine are studied using density functional theory. The infinite system characterized by exact translational-rotational symmetry is examined in vacuum using the BLYP exchange-correlation functional. Geometry analysis in terms of hydrogen bond strength and total energies of the different conformers are presented. The structural changes due to the presence of the serine side chain are identified comparing the polyserine and polyglycine chains. The rotational energy curves of the side chain are presented for both investigated helices. Band structures of polyserine and polyglycine conformers are also compared.     

Chemoenzymatic synthesis of highly enantiomerically enriched secondary alcohols with a thiazolic core

Stereoselective preparative enzymatic acylation and hydrolysis/methanolysis of various C-substituted rac-thiazol-2-yl-methanols were achieved for the preparation of enantiopure or enantiomerically enriched, naturally occurring 2-hydroxymethylthiazoles. The absolute configurations of the resulting secondary alcohols were determined by a detailed ¹H NMR study of Mosher’s derivatives.     

Exploring and characterizing the folding processes of Lys- and Arg-containing Ala-based peptides: a molecular dynamics study

In this study, molecular dynamics simulations were carried out on Lys- and Arg-containing Ala-based peptides (i.e. Ace-(AAAAK)(n)A-NH(2) and Ace-(AAAAR)(n)A-NH(2), where n=1-4), in order to explore and characterize their folding processes. For the oligopeptides, the evolution of α-helical structure with regard to the whole conformation, as well as to each residue was investigated, and the helix-forming propensities were characterized. On the basis of the helicity curves, representing the alteration of average helicity as a function of time, the typical time values describing the folding processes and subprocesses were identified. In the case of each peptide, the evolution and role of helix-stabilizing, non-local and side-chain-to-backbone H-bonds were examined. The appearing i←i+4 H-bonds pointed out the role of these interactions in the stabilization of α-helical conformations, while the occurring i←i+3 H-bonds indicated the presence of β-turn or 3(10)-helical structures. Studying the formation and role of non-local and side-chain-to-backbone H-bonds led to the observation that these types of interactions produced an effect on the evolution of helical conformations, as well as on the folding processes.     

Aconitum lipo-alkaloids--semisynthetic products of the traditional medicine

The term lipo-alkaloid is used for C19 aconitane alkaloids containing one or two long-chain fatty acid residues. Lipo-alkaloids are transesterified derivatives of the most toxic and highly effective diester-type diterpene alkaloids, such as aconitine, hypaconitine, mesaconitine. Lipo-alkaloids are native minor compounds of aconite drugs, but their amount significantly increases after traditional processing, which is a general method in the Far Eastern traditional medicinal systems. Analytical works demonstrated that cautious processing (usually boiling) of crude aconite roots decreases the amount of normal diterpene alkaloids and increases the concentration of lipo-alkaloids resulting in the reduction of toxicity of the drugs. Many papers reported that lipo-alkaloids occur as a complex mixture in the drugs, and the isolation of the individual components is extremely difficult. These compounds have been identified using highly sensitive analytical methods (HPLC-MS, NMR), and semisynthetic approaches have been developed to ensure lipo-alkaloids in pure form for pharmacological studies. This review summarizes the structure, chemistry, semisynthesis, analytics and bioactivities of lipo-alkaloids. On the basis of 32 references this is the first comprehensive study on this topic, covering the data of 173 compounds.     

Proton Diffusion andT1Relaxation in Polyacrylamide Gels: A Unified Approach Using Volume Averaging

The structure of polyacrylamide gels was studied using proton spin–lattice relaxation and PFG diffusion methods. Polyacrylamide gels, with total polymer concentrations ranging from 0.25 to 0.35 g/ml and crosslinker concentrations from 0 to 10% by weight, were studied. The data showed no effect of the crosslinker concentration on the diffusion of water molecules. The Ogston–Morris and Mackie–Meares models fit the general trends observed for water diffusion in gels. The diffusion coefficients from the volume averaging method also fit the data, and this theory was able to account for the effects of water-gel interactions that are not accounted for in the other two theories. The averaging theory also did not require the physically unrealistic assumption, required in the other two theories, that the acrylamide fibers are of similar size to water molecules. Contrary to the diffusion data,T₁relaxation measurements showed a significant effect of crosslinker concentration on the relaxation of water in gels. The model developed using the Bloch equations and the volume averaging method described the effects of water adsorption on the gel medium on both the diffusion coefficients and the relaxation measurements. In the proposed model the gel medium was assumed to consist of three phases (i.e., bulk water, uncrosslinked acrylamide fibers, and a bisacrylamide crosslinker phase). The effects of the crosslinker concentration were accounted for by introducing the proton partition coefficient,K^eq, between the bulk water and crosslinker phase. The derived relaxation equations were successful in fitting the experimental data. The partition coefficient,K^eq, decreased significantly as the crosslinker concentration increased from 5 to 10% by weight. This trend is consistent with the idea that bisacrylamide tends to form hydrophobic regions with increasing crosslinker concentration.     

First principle computational study on the full conformational space of L-proline diamides

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-NH2 [I], HCO-Pro-NH-Me [II], MeCO-Pro-NH2 [III], and MeCO-Pro-NH-Me [IV], representing a systematic variation in the protecting N- and C-terminal groups. Three previously located backbone conformations, gammaL, epsilonL, and alphaL, 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-NH2 [I] was also analyzed in terms of potential energy surfaces (PESs). Thermodynamic functions were also calculated for HCO-Pro-NH2 [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.     

Binding sites of amyloid beta-peptide in cell plasma membrane and implications for Alzheimer's disease

The binding of amyloid beta peptides (Abeta) to plasma membranes appears to be a promising point of intervention in the events leading to the development of Alzheimer's disease (AD). This binding has been studied as regards the direct toxicity of Abeta on neurons, and the activation of a local inflammation phase involving microglia. By virtue of its structure, Abeta is able to bind to a variety of biomolecules, including lipids, proteoglycans and proteins. This review focuses on the membrane proteins that can mediate the interaction between Abeta and the plasma membranes in AD. On neurons, these are APP (amyloid precursor protein), the NMDA-R (N-methyl-D-aspartate receptor), integrins, the alpha7nicotinic acetylcholine receptor (alpha7nAChR), the P75 neurotrophin receptor (P75NTR) and the CLAC-P/collagen type XXV (collagen-like Alzheimer amyloid plaque component precursor/collagen XXV). On glial cells, FPRL1 (formyl peptide receptor-like 1), the scavenger receptors A, BI (SR-A, SR-BI) and CD36, a complex involving CD36, alpha(6)beta(1)-integrin and CD47, and heparan sulfate proteoglycans have been reported to bind Abeta. It should be noted that integrins, RAGE (receptor for advanced glycosylation end-products), the Serpin-enzyme complex receptor (SEC-R) and the insulin receptor can bind Abeta and are present on neurons and on glial cells. After a presentation of the structure and the function of each of these proteins, the method used to prove their binding to Abeta is described, and the implication of this binding in AD is discussed. Finally, it is underlined that multireceptor complexes containing integrins may be involved in this interaction.     

Folded and unfolded conformations of the omega-3 polyunsaturated fatty acid family: ch(3)ch(2)[ch=chch(2)](b)[ch(2)](m)cooh: first principles study

Polyunsaturated fatty acids (PUFA) like stearidonic acid (SDA;18:4 n-3) eicosapentaenoic acid (EPA; 20:5 n-3), and docosahexaenoic acid (DHA; 22:6 n-3) and its chain fragment models were studied at B3LYP/6-31G(d) levels of theory. Significant conformations for the cis and trans isomers were selected to obtained the thermodynamic functions (DeltaH, DeltaS, DeltaG) for the cis-trans isomerization and for folding using the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) level of theory. The structural analysis shows that there are significant differences in thermodynamic function of the trans- and cis-PUFAs. The trans-cis isomerization energy values reinforce the consistency and the relative accuracy of theoretical model calculations. The observed flexibility of naturally cis PUFAs could be explained by a very special "smooth basin" PES of the motif of sp(2)-sp(3)-sp(2) hybrid states as reported previously (J. Phys. Chem. A 2005, 109, 520-533). We assumed that intrinsic thermodynamic functions may describe this flexible folding process. The folding enthalpy as well as the folding entropy suggests that there is a new role of the cis-PUFAs in membranes: these cis isomers may have a strong influence on membrane stability and permeability. The average length of the cis helix and beta PUFA was approximated. The difference between the lengths of these two structures is approximately 10 A.     

Comparison of HF,HF + MP2, LDA,BLYP, and B3LYP band structures of the homopolypeptides

Ab initio HF, HF + MP2, LDA DFT, BLYP DFT, and B3LYP DFT calculations are compared in the case of 19 homopolypeptides in their β pleated sheet conformation. The results show that the B3LYP method provides good results for the fundamental gaps, as compared with the values estimated on the basis of available UV spectra and intermediate exciton calculations for PolyGly and PolyAla. The HF method gives the best agreement, using Koopman's theorem for the ionization potential, taking the calculated VB_max values in the HF case if one compares them with the experimental ionization potentials of the 19 amino acids measured by mass spectroscopy. Finally, how these methods might be improved to determine the most stable conformations of the homopolypeptides is outlined. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004