The Linear Tripeptide L-Alanylglyeyl-L- alanine

L-Alanylglycyl-L-alanine, C8H15N3O4, exists as zwitter-ion in the crystal with the N terminus protonated and the C terminus in an ionized form, Both the peptide units are in trans configurations and deviate significantly from planarity. Backbone torsion angles are psi(1)=172.7(2), omega(1)=-178.2(2), phi(2)=91.7(2), phi(2)=-151.9(2), omega(2)=-176.9(2), phi(3)=-71.3(2), phi(31)=-7.0(3) and psi(32) 172.4(2)degrees. The protonated NH3+ group forms three hydrogen bonds with atoms of symmetry-related molecules.

Helix-coil stability constants for amino acids in nonaqueous solvents. Studies of random poly(-benzyl-L-glutamate-co-L-alanine) and poly(-benzyl-L-glutamate-co-L-leucine) in a mixed solvent

The host-guest technique has been applied to the determination of the helix-coil stability constants of two naturally occurring amino acids, L-alanine and L-leucine, in a nonaqueous solvent system. Random copolymers containing L-alanine and L-leucine, respectively, as guest residues and -benzyl-L-glutamate as the host residue were synthesized. The polymers were fractionated and characterized for their amino acid content, molecular weight, and helix-coil transition behavior in a dichloroacetic acid (DCA)-1,2-dichloroethane (DCE) mixture. Two types of helix-coil transitions were carried out on the copolymers: solvent-induced transitions in DCA-DCE mixtures at 25°C and thermally induced transitions in a 82:18 (wt %) DCA-DCE mixture. The thermally induced transitions were analyzed by statistical mechanical methods to determine the Zimm-Bragg parameters, and s, of the guest residues. The experimental data indicate that, in the nonaqueous solvent, the L-alanine residue stabilizes the -helical conformation more than the L-leucine residue does. This is in contrast to their behavior in aqueous solution, where the reverse is true. The implications of this finding for the analysis of helical structures in globular proteins are discussed.

New ternary copper(II) complexes of L-alanine and heterocyclic bases: DNA binding and oxidative DNA cleavage activity

Four new ternary copper(II) complexes of alpha-amino acid having polypyridyl bases of general formulation [Cu(L-ala)(B)(H2O)](X)(1-4), where L-ala is L-alanine, B is an N,N-donor heterocyclic base, viz. 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2) and 5,6-phenanthroline dione (dione, 3), dipyrido[3,2:2',3'-f] quinoxaline (dpq, 4), and X = ClO4-/NO3- are synthesized, characterized by various spectroscopic and X-ray crystallographic methods. The complexes show a distorted square-pyramidal (4 + 1) CuN3O2 coordination geometry. The one-electron paramagnetic complexes (1-4) display a low energy d-d band near 600 nm in aqueous medium and show a quasi-reversible cyclic voltammetric response due to one-electron Cu(II)/Cu(I) reduction near - 100 mV (versus SCE) in DMF-0.1 M TBAP. Binding interactions of the complexes with calf thymus DNA (CT-DNA) were investigated by UV-Vis absorption titration, ethidium bromide displacement assay, viscometric titration experiment and DNA melting studies. All the complexes barring the complexes 1 and 3 are avid binder to the CT-DNA in the DNA minor groove giving an order: 4 > 2 >>>1, 3. The complexes 2 and 4 show appreciable chemical nuclease activity in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent. Hydroxyl radical was investigated to be the DNA cleavage active species. Control experiments in the presence of distamycin-A show primarily minor groove-binding propensity for the complexes 2 and 4 to the DNA.

Potential functions for hydrogen bond interactions - IV. Minimum Energy Conformation of the α-Helical Structure of PoIy-L-Alanine

Making use of the empirical potential functions for peptide NH .. O bonds, developed in this laboratory, the relative stabilities of the rightand left-handed α-helical structures of poly-L-alanine have been investigated, by calculating their conformational energies (V). The value of Vmin of the right-handed helix (αP) is about - 10.4 kcal/mole, and that of the left-handed helix (αM) is about - 9.6 kcal/mole, showing that the former is lower in energy by 0.8 kcal/mole. The helical parameters of the stable conformation of αP are n ∼ 3.6 and h ∼ 1.5 Å. The hydrogen bond of length 2.85 Å and nonlinearity of about 10° adds about 4.0 kcal/ mole to the stabilising energy of the helix in the minimum enregy region. The energy minimum is not sharply defined, but occurs over a long valley, suggesting that a distribution of conformations (φ{symbol}, ψ) of nearly the same energy may occur for the individual residues in a helix. The experimental data of a-helical fibres of poly-L-alanine are in good agreement with the theoretical results for αP. In the case of proteins, the mean values of (φ{symbol}, ψ) for different helices are distributed, but they invariably occur within the contour for V = Vmin + 2 kcal/mole for αP.

Remarkable Regioisomer Control in the Hydrogel Formation from a Two-Component Mixture of Pyridine-End Oligo(p-phenylenevinylene)s and N-Decanoyl-L-alanine

N-Decanoyl-L-alanine (DA) was mixed with either colorless 4,4-bipyridine (BP) or various derivatives such as chromogenic oligo(p-phenylenevinylene) (OPV) functionalized with isomeric pyridine termini in specific molar ratios. This mixtures form salt-type gels in a water/ethanol (2:1, v/v) mixture. The gelation properties of these two-component mixtures could be modulated by variation of the position of the N atom of the end pyridyl groups in OPVs. The presence of acid-base interactions in the self-assembly of these two-component systems leading to gelation was probed in detail by using stoichiometry-dependent UV/Vis and FTIR spectroscopy. Furthermore, temperature-dependent UV/Vis and fluorescence spectroscopy clearly demonstrated a J-type aggregation mode of these gelator molecules during the sol-to-gel transition process. Morphological features and the arrangement of the molecules in the gels were examined by using scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction (XRD) techniques. Calculation of the length of each molecular system by energy minimization in its extended conformation and comparison with the XRD patterns revealed that this class of gelator molecules adopts lamellar organizations. Rheological properties of these two-component systems provided clear evidence that the flow behavior could be modulated by varying the acid/amine ratio. Polarized optical microscopy (POM), differential scanning calorimetry (DSC), and XRD results revealed that the solid-phase behavior of such two-component mixtures (acid/base=2:1) varied significantly upon changing the proton-acceptor part from BP to OPV. Interestingly, the XRD pattern of these acid/base mixtures after annealing at their associated isotropic temperature was significantly different from that of their xerogels.

Regulation of L-alanine dehydrogenase in Rhizobium leguminosarum bv. viciae and its role in pea nodules

Alanine dehydrogenase (AldA) is the principal enzyme with which pea bacteroids synthesize alanine de novo. In free-living culture, AMA activity is induced by carboxylic acids (succinate, malate, and pyruvate), although the best inducer is alanine. Measurement of the intracellular concentration of alanine showed that AldA contributes to net alanine synthesis in laboratory cultures. Divergently transcribed from aldA is an AsnC type regulator, aldR. Mutation of aldR prevents induction of AldA activity. Plasmid-borne gusA fusions showed that aldR is required for transcription of both aldA and aldR; hence, AldR is autoregulatory. However, plasmid fusions containing the aldA-aldR intergenic region could apparently titrate out AldR, sometimes resulting in a complete loss of AldA enzyme activity. Therefore, integrated aldR::gusA and aldA::gusA fusions, as well as Northern blotting, were used to confirm the induction of aldA activity. Both aldA and aldR were expressed in the II/III interzone and zone III of pea nodules. Overexpression of aldA in bacteroids did not alter the ability of pea plants to fix nitrogen, as measured by acetylene reduction, but caused a large reduction in the size and dry weight of plants. This suggests that overexpression of aldA impairs the ability of bacteroids to donate fixed nitrogen that the plant can productively assimilate. We propose that the role of AldA may be to balance the alanine level for optimal functioning of bacteroid metabolism rather than to synthesize alanine as the sole product of N-2 reduction.

Evidence that L-glutamine is better than L-alanine as gluconeogenic substrate in perfused liver of weaned fasted rats submitted to short-term insulin-induced hypoglycaemia

Gluconeogenesis in livers from overnight fasted weaned rats submitted to short-term insulin-induced hypoglycaemia (IIH) was investigated. For this purpose, a condition of hyperinsulinemia/hypoglycaemia was obtained with an intraperitoneal (ip) injection of regular insulin (1.0 U kg(-1)). Control group (COG group) received ip saline. The studies were performed 30 min after insulin (IIH group) or saline (COG group) injection. The livers from IIH and COG rats were perfused with L-alanine (5 mM), L-lactate (2 mM)), L-glutamine (10 mM) or glycerol (2 mM). Hepatic glucose, L-lactate and pyruvate production from L-alanine was not affected by IIH. In agreement with this result, the hepatic ability in producing glucose from L-lactate or glycerol remained unchanged (IIH group vs. COG group). However, livers from IIH rats showed higher glucose production from L-glutamine than livers front COG rats and, in the IIH rats, the production of glucose from L-glutamine was higher than that front L-alanine. The higher glucose production in livers from the IIH group. when compared with the COG group was due to its entrance further on gluconeogenic pathway. Taken together. the results suggest that L-glutamine is better than L-alanine, as gluconeogenic substrate in livers of hypoglyceaemic weaned rats. Copyright (C) 2008 John Wiley & Sons. Ltd.

Synthesis and anti-corrosion performance of Adenine-L-Alanine ramification

In this paper, a new amino acid derivative, namely Adenine-L-Alanine ramification (ALAR) was synthesized and investigated as a green corrosion inhibitor for X80 pipeline steel in 0.1 mol/L hydrochloric acid solution using the weight loss, AC impedance, and polarization curve method. The structure of the derivative was characterized by IR and UV–vis spectrum. The weight loss and AC impedance found that the inhibition efficiency increased with the increase in concentration of the inhibitor but decreased with rise in temperature, the corrosion inhibition efficiency attains 91.26% in 8 × 10−2 g/L concentration at 30 °C. The polarization studies showed that the studied amino acid derivative can be used as a corrosion inhibitor. The surface of inhibited and uninhibited specimens was analyzed by scanning electron microscopy and the adsorption of the inhibitor on the mild steel surface obeys Langmuir adsorption isotherm. The quantum chemical descriptors such as the energy of highest occupied molecular orbital, energy of lowest unoccupied molecular orbital were calculated and the inhibition mechanism can be analyzed by the distribution of electrons. Analysis indicated that the inhibitor molecular and empty d orbital of metal forms the coordination bond, covers on the surface of metal, and prevents corrosion reaction.

Response of L-alanine and 2-methylalanine minidosimeters for K-Band (24 GHz) EPR dosimetry

Minidosimeters of L-alanine and 2-methylalanine (2MA) were prepared and tested as potential candidates for small radiation field dosimetry. To quantify the free radicals created by radiation a K-Band (24 GHz) EPR spectrometer was used. X-rays provided by a 6 MV clinical linear accelerator were used to irradiate the minidosimeters in the dose range of 0.5-30 Gy. The dose-response curves for both radiation sensitive materials displayed a good linear behavior in the dose range indicated with 2MA being more radiation sensitive than L-alanine. Moreover, 2MA showed a smaller LLD (lower limit detection) value. The proposed system minidosimeter/K-Band spectrometer was able to detect 10 Gy EPR spectra with good signal-to-noise ratio (S/N). The overall uncertainty indicates that this system shows a good performance for the detection of dose values of 20 Gy and above, which are dose values typically used in radiosurgery treatments. (c) 2007 Elsevier B.V. All rights reserved.

Caractérisation d'un organogel à base d'un dérivé amphiphile de la L-alanine

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Organogel à base d'un dérivé de la L-alanine pour la libération prolongée de leuprolide : étude pharmacocinétique et pharmacodynamique chez le rat

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Caractérisation d'un organogel à base d'un dérivé amphiphile de la L-alanine

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Organogel à base d'un dérivé de la L-alanine pour la libération prolongée de leuprolide : étude pharmacocinétique et pharmacodynamique chez le rat

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The neurotoxin β-N-methylamino-L-alanine (BMAA) : Sources, bioaccumulation and extraction procedures

β-methylamino-L-alanine (BMAA) is a neurotoxin linked to neurodegeneration, which is manifested in the devastating human diseases amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s disease. This neurotoxin is known to be produced by almost all tested species within the cyanobacterial phylum including free living as well as the symbiotic strains. The global distribution of the BMAA producers ranges from a terrestrial ecosystem on the Island of Guam in the Pacific Ocean to an aquatic ecosystem in Northern Europe, the Baltic Sea, where annually massive surface blooms occur. BMAA had been shown to accumulate in the Baltic Sea food web, with highest levels in the bottom dwelling fish-species as well as in mollusks. One of the aims of this thesis was to test the bottom-dwelling bioaccumulation hypothesis by using a larger number of samples allowing a statistical evaluation. Hence, a large set of fish individuals from the lake Finjasjön, were caught and the BMAA concentrations in different tissues were related to the season of catching, fish gender, total weight and species. The results reveal that fish total weight and fish species were positively correlated with BMAA concentration in the fish brain. Therefore, significantly higher concentrations of BMAA in the brain were detected in plankti-benthivorous fish species and heavier (potentially older) individuals. Another goal was to investigate the potential production of BMAA by other phytoplankton organisms. Therefore, diatom cultures were investigated and confirmed to produce BMAA, even in higher concentrations than cyanobacteria. All diatom cultures studied during this thesis work were show to contain BMAA, as well as one dinoflagellate species. This might imply that the environmental spread of BMAA in aquatic ecosystems is even higher than previously thought. Earlier reports on the concentration of BMAA in different organisms have shown highly variable results and the methods used for quantification have been intensively discussed in the scientific community. In the most recent studies, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the instrument of choice, due to its high sensitivity and selectivity. Even so, different studies show quite variable concentrations of BMAA. In this thesis, three of the most common BMAA extraction protocols were evaluated in order to find out if the extraction could be one of the sources of variability. It was found that the method involving precipitation of proteins using trichloroacetic acid gave the best performance, complying with all in-house validation criteria. However, extractions of diatom and cyanobacteria cultures with this validated method and quantified using LC-MS/MS still resulted in variable BMAA concentrations, which suggest that also biological reasons contribute to the discrepancies. The current knowledge on the environmental factors that can induce or reduce BMAA production is still limited. In cyanobacteria, production of BMAA was earlier shown to be negative correlated with nitrogen availability – both in laboratory cultures as well as in natural populations. Based on this observation, it was suggested that in unicellular non-diazotrophic cyanobacteria, BMAA might take part in nitrogen metabolism. In order to find out if BMAA has a similar role in diatoms, BMAA was added to two diatom species in culture, in concentrations corresponding to those earlier found in the diatoms. The results suggest that BMAA might induce a nitrogen starvation signal in diatoms, as was earlier observed in cyanobacteria. However, diatoms recover shortly by the extracellular presence of excreted ammonia. Thus, also in diatoms, BMAA might be involved in the nitrogen balance in the cell.