Synthesis of two peptides of α-bungarotoxin and the participation of the amino acid residue Trp-28 of the neurotoxin in the antigenicity of the molecule

Using the method of solid-phase peptide synthesis, two peptides have been synthesized, one of which corresponds to the central ring structure of -bungarotoxin (-BTX), while the second has in position 28 a Gly residue in place of the Trp in the first peptide, and their interrelationship with antitoxin antibodies has been investigated. It has been shown that the amino acid residue Trp-28 of -BTX, which is the contact residue in binding with the acetylcholine receptor, also participates directly in binding with the active centers of antibodies to -BTX.Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 628–631, July–August, 1997.     

Glycoconjugates of amino acids. Preparation throughN-alkylation of amino acids withN-chloroacetyl-β-glycopyranosylamines

Monoalkylation of amino acids of different structural types withN-chloroacetyl-glycosylamines was shown to be applicable for the preparation of glycoconjugates containing β-d-galactose,N-acetyl-β-d-glucosamine, β-d-mannose, and lactose residues. The glycoconjugates were synthesized from amino acids with secondary (sarcosine,l-proline) or primary (l-2- and 4-aminobutyric acids,l-tryptophan) amino groups as well as from various amino dicarboxylic acids (N-methyl-dl-aspartic,dl-aspartic,l-glutamic, anddl-2-aminoadipic acids). The derivatives obtained may be of interest for glycotargeting of physiologically active compounds of this series. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1377–1380, July, 1999.     

Aminopyridines as amino components in the catalytic synthesis of α-aminophosphonates

6h-Aminophosphonates containing alicyclic, aromatic, and heterocyclic fragments were obtained in high yields by the Kabachnick—Fields reaction of the corresponding carbonyl compounds with 2-, 3- and 4-aminopyridines and diethyl phosphite using tetra- tert-butyl- phthalocyanine aluminum chloride as the catalyst. 2-, 3-, 4-Aminopyridines were found to vary in their reactivity with ketones and diethyl phosphite in the catalytic three-component one-pot process.     

Early introduction of the amino group to the C27–C35 building block of Eribulin

A new synthetic strategy towards the C27–C35 subunit of Eribulin (1) has been devised to include a protected 1,2-amino alcohol at C34–C35. Early introduction of the C35 amino group in the synthesis of 1 increases the efficiency of the route. This new approach can be accomplished on a multi-gram scale and allows for the successful synthesis of Eribulin.     

The amino terminus of cGMP-dependent protein kinase Iβ increases the dynamics of the protein's cGMP-binding pockets

The type I cGMP-dependent protein kinases play critical roles in regulating vascular tone, platelet activation and synaptic plasticity. PKG I α and PKG Iβ differ in their first ~100 amino acids giving each isoform unique dimerization and autoinhibitory domains with identical cGMP-binding pockets and catalytic domains. The N-terminal leucine zipper and autoinhibitory domains have been shown to mediate isoform specific affinity for cGMP. PKG Iα has a >10 fold higher affinity for cGMP than PKG Iβ, and PKG Iβ that is missing its leucine zipper has a three-fold decreased affinity for cGMP. The exact mechanism through which the N-terminus of PKG alters cGMP-affinity is unknown. In the present study, we have used deuterium exchange mass spectrometry to study how PKG Iβ's N-terminus affects the conformation and dynamics of its cGMP-binding pockets. We found that the N-terminus increases the rate of deuterium exchange throughout the cGMP-binding domain. Our results suggest that the N-terminus shifts the conformational dynamics of the binding pockets, leading to an "open" conformation that has an increased affinity for cGMP.     

Does amino acid sequence determine the properties of Aβ dimer?

The effect of random reshuffling of amino acids on the properties of dimers formed by Aβ peptides is studied using replica exchange molecular dynamics and united atom implicit solvent model. We show that thermodynamics of dimer assembly and the dimer globule-like state are not affected by sequence permutation. Furthermore, sequence reshuffling does not change the distributions of non-local interactions and, to a large extent, amino acids in the dimer volume. To rationalize these results, we demonstrate that Gaussian statistics applies surprisingly well to the end-to-end distances of the peptides in the dimer implying that non-bonded interactions between distant along the chain amino acids are effectively screened. This observation suggests that peptides in the dimer behave as ideal chains in polymer melt, in which amino acids lose their "identity" and therefore the memory of sequence position. As a result large-scale properties of the dimer become universal or sequence independent. Comparison of our simulations with the prior theoretical studies and their implications for experiments are discussed.     

Synthesis of bi- and tervalent ligands of galectins,derivatives of β-lactosylamine,with the amino group in the terminal position of the spacer

A method for the synthesis of glycoclusters by N-alkylation of N-glycyl-β-lactosylamine with N-chloroacetyl derivatives of β-lactosylamine and N,N’-iminodiacetyldilactosylamine has been developed. The glycoclusters obtained with two and three lactosylamine residues with the amino group in the spacer were found to be suitable for further conjugation with carboxy-containing physiologically active compounds. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 647–651, March, 2008.     

Chiroptical study of α-aliphatic amino acid films in the vacuum ultraviolet region

A series of natural circular dichroism (CD) and absorption spectra for films of α-aliphatic amino acids--such as alanine, aminobutyric acid, norvaline, norleucine, valine, leucine, and isoleucine--in the vacuum ultraviolet (VUV) region were observed with the absolute values of optical constants at the undulator-based CD beamline TERAS BL5. Preliminary predictions of some CD spectra were also performed, based on quantum-chemical calculations using the crystal structure. Although the absorption spectra show similar features to each other, significant differences between the CD spectra were found, especially in the 7-8 eV region. The CD spectra of aliphatic amino acids with branched alkyl groups in the side-chain--such as valine, leucine, and isoleucine--exhibit strong negative CD peaks in this energy region. In contrast, the corresponding CD peaks were weak or absent in the spectra of amino acids with straight alkyl groups. Our simple calculation, and the absorption spectra of alkanes, suggest that this difference partly originates from the contribution of the alkyl group. Clear discrepancies between the CD spectra of these amino acids in solutions and those in the solid state were also observed; this is probably caused by the different molecular structures in each state. Our results clearly indicated that CD spectra in the VUV region were very sensitive to the conformations of chiral molecules.     

Microwave-assisted reaction of peptide formation by amino acid with phosphate:Exploration of the most possible channels for the origin of life

The formation of peptides and then protein by small abiological molecules clusters such as amino acid is a key stage in the origin of life[1]. More and more ex- perimental results showed that phosphate plays an important role in the formation of biomolecules in prebiotic chemical evolution. The principal reservoirs of biochemical energy are phosphates (such as ATP). The peculiar role of phosphates in contemporary life might suggest its essential role in prebiotic energy conversion, syntheses …     

8-AminoBODIPYs: cyanines or hemicyanines? The effect of the coplanarity of the amino group on their optical properties

The role of the amino group twisting ability in the BODIPY photophysics for nonsterically hindered and constrained molecular structures was studied. When a coplanar disposition of the amino and the BODIPY core is feasible, a hemicyanine-like delocalized π-system gives rise to novel blue and efficient BODIPY laser dyes. The key role of such rotamer is confirmed by newly synthesized derivatives where the amino and the BODIPY core are electronically decoupled by steric repulsions.     

Microbial production of natural poly amino acid

Three kinds of poly amino acids, poly-γ-glutamic acid, poly(ε-L-lysine) and multi-L-arginyl-poly (L-aspartic acid) can be synthesized by enzymatic process independently from ribosomal protein biosynthesis pathways in microorganism. These biosynthesized polymers have attracted more and more attentions because of their unique properties and various applications. In this review, the current knowledge on the biosynthesis, biodegradations and applications of these three poly amino acids are summarized.     

Systematic study of the transfer of amino acids across the water/1,2-dichloroethane interface facilitated by dibenzo-18-crown-6

Facilitated ion transfer reactions of 20 amino acids with dibenzo-18-crown-6 (DB18C6) at the water/1,2-dichloroethane (W/DCE) interfaces supported at the tips of micro- and nano-pipets were investigated systematically using cyclic voltammetry. It was found that there were only 10 amino acids, that is, Leu, Val, lie, Phe, Trp, Met, Ala, Gly, Cys, Gin (in brief), whose protonated forms as cations can give well-defined facilitated ion transfer voltammograms within the potential window, and the reaction pathway was proven to be consistent with the transfer by interfacial complexation/dissociation (TIC/TID) mechanisms. The association constants of DB 18C6 with different amino acids in the DCE (β0), and the kinetic parameters of reaction were evaluated based on the steady-state voltammetry of micro- or nano-pipets, respectively. The experimental results demonstrated that the selectivity of complexation of protonated amino acid by DB18C6 compared with that of alkali metal cations was low, which can be attribu     

Is X-ray absorption spectroscopy sensitive to the amino acid composition of functional proteins?

We report, compare, and analyze near-edge X-ray absorption fine structure (NEXAFS) spectra of powder samples of four different functional proteins, namely, lysozyme, ovalbumin, bovine serum albumin, and type-I collagen, at all relevant absorption edges. The spectra of all of the above proteins were found to be quite similar and to exhibit minor differences only. Nevertheless, despite the general similarity, the spectra of the individual proteins are distinguishable, and some of the respective differences clearly correlate with their amino acid compositions. Further factors affecting the NEXAFS spectra of proteins beyond the building block approach are discussed.     

On-line sample stacking of peptides in capillary electrophoresis for the study of prebiotic reactions between α,α-dialkylated amino acids and amino acid N-carboxyanhydrides

The reaction between α,α-dialkylated amino acids and amino acid N-carboxyanhydrides is slow leading to low concentrations of products (peptides). The detection by capillary electrophoresis of the analytes contained in such samples is therefore a challenging issue. In this work, on-line sample pre-concentration methods based on field-amplified sample stacking have been implemented and compared. Because of the high ionic strength present in the sample matrix, samples were diluted with an organic solvent prior to analysis to decrease the sample conductivity. Different modes of sample injection (field amplified sample injection (FASI), hydrodynamic normal sample stacking (NSS) or large volume sample stacking (LVSS)) were compared. Pre-concentration factors of 20 for FASI, about 30–40 for NSS and 60 for LVSS were obtained for the analysis of (l,l) dipeptide of valine in a large excess of isovaline and 0.2 M of ionic strength. For LVSS application and resolution optimisation, a new non-covalent coating based on the partial modification of the capillary surface was used to tune the electroosmotic flow magnitude and to pump the sample matrix out of the capillary. This on-line sample pre-concentration step allowed confirming that oligopeptides including α,α-dialkylated amino acids are formed during the reaction between α,α-dialkylated amino acids and N-carboxyanhydride amino acids.     

BINOL-derived phosphoramidites in asymmetric hydrogenation: can the presence of a functionality in the amino group influence the catalytic outcome?

In discovering the remarkable catalytic properties of BINOL-derived phosphoramidites (binoP-NR(2)), Dutch researchers recently achieved a long-awaited breakthrough in asymmetric catalysis. For the first time, easily accessible monodentate chiral P(III) ligands turned out to provide high enantioselectivities when used in rhodium-catalysed olefin hydrogenation. The simplest ligand representative of this family is MonoPhos, which can be made straightforwardly from BINOL and hexamethylphosphorous triamide. Since the first publication dealing with such catalysts (J. Am. Chem. Soc., 2000), a variety of binoP-NRR' ligands have been reported in which the amino group bears a functional substituent or a stereogenic centre. This critical review examines the impact of the presence of such a functionality in the amino group on catalytic olefin hydrogenation reactions.     

Synthesis of novel β2,2-amino acid from D-mannose and attempted synthesis of peptides from the amino acid

The study describes the synthesis of new α,α-disubstituted β-amino acid (β^2,2-Caa) and attempts the synthesis of peptides from it. The β^2,2-Caa was prepared from D-(+)-mannose, using crossed aldol and Cannizzaro reactions.     

Catalytic α-allylation of unprotected amino acid esters

Catalytic α-allylation of unprotected amino acid esters to produce α-quaternary α-allyl amino acid esters is reported. Catalytic loadings of picolinaldehyde and Ni(II) salts induce preferential reactivity at the enolizable α-carbon of amino acid esters over the free nitrogen with electrophilic palladium π-allyl complexes. Fourteen examples are given. Additionally, the use of chiral ligands to access enantioenriched α-quaternary amino acid esters from racemic precursors is demonstrated by the enantioselective synthesis of α-allyl phenylalanine methyl ester from racemic phenylalanine methyl ester.