Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder

The effective intervention strategy for autism spectrum disorder(ASD)are currently limited.Herein,we attempted to evaluate the potential of L-proline(Pro),a multifunctional amino acid,in ameliorating autismlike behaviors and clarify the molecular mechanisms involved by using the typical valproic acid(VPA)-induced mouse model of ASD.Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice.The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition.The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex(PFC)induced by VPA exposure.RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease,neuroactive ligand-receptor interaction,oxidative phosphorylation,and mitogen activated protein kinase signaling pathway.Overall,dietary Pro supplementation may be a promising intervention strategy for ASD.

Amide Ionic Liquids(AILs)/L-Proline Synergistic Catalyzed Asymmetric Mannich Reactions

Amide ionic liquids （MLs）/L-proline synergistic catalyzed Mannich reactions of isovaleraldehyde, methyl ketones, and aromatic amines were carried out in moderate to high yields （ up to 96% ） and high stereo selectivities （ 〉99% e. e. ）. The products were easily isolated by extraction; and the catalyst system was readily recycled at least thrice without significant loss of efficiency. The scope of the substrates was studied and the interpretation of the manifest improvement of the reaction rates and enantio-selectivity of the novel catalyst system was speculated.

L-Proline as an efficient and reusable promoter for the synthesis of coumarins in ionic liquid

The effect of L-proline as a promoter on the condensation reaction of salicylaldehyde or its derivatives with ethyl acetoacetate in neutral ionic liquid [emim]BF4 was studied. All reactions were carried out under mild reaction conditions and achieved high yields. Moreover, the ionic liquid containing L-proline could be recycled and reused for several times without noticeably decreasing in productivity. The results show that the L-proline-[emim]BF4 system has a potential in contribution to the development of environmentally friendly and inexpensive processes in organic syntheses.

Synthesis of Novel Monophosphoramidite Ligands Derived from L-Proline for Rh-catalyzed Asymmetric Hydrogenation of α-Dehydroamino Acid Esters

Two novel monophosphoramidites were synthesized through a five-step transformation from commercially available L-proline. In the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives, ligand （Sc,Rα）-1b showed good enantioselectivity and up to 91% e.e. was obtained.

Electrocatalytic Determination of Dopamine in the Presence of Ascorbic Acid by Poly-L-proline and Ferricyanide Compound Film Modified Electrode

A novel biosensor was fabricated by the electrochemical polymerization of poly-L-proline（P-LP） and ferricyanide（FC） to form a compound film on a glassy carbon electrode（GCE）. The compound film modified electrode（P-LP/FC/GCE） shows electrocatalytic activity toward dopamine（DA） in a phosphate buffer solution（PBS, pH = 4.0） with a diminution of the overpotential and an increase in peak current. P-LP/FC/GCE was used to study the electrocatalytic oxidation of DA and ascorbic acid（AA） by means of cyclic voltammetry（CV）, differential pulse voltammetry（DPV） and amperometric i-t curve techniques. The overlapping anodic peaks of DA and AA were resolved into two well-defined voltammetric peaks in CV and DPV with the potential differences of about 200 and 225 mV, respectively. The peak current of DA is linearly change with the concentration of DA in a range of 1 × 10^-7 to 1.14 × 10^-4 mol/L with the correlation coefficient of 0.9997. The detection limit is 4.4~10-8 mol/L（S/N=3）. P-LP/FC/GCE exhibited an excellent selectivity, sensibility and stability for the determination of DA, and can be applied to the determination of dopamine injections with satisfied results.

Electron Communication Between Electrode and Dye-Linked L-Proline Dehydrogenase in Organized Layer-by-Layer Multilayer Film

Multilayer film was fabricated on an electrode surface by alternate layer-by-layer（LBL） adsorption of polycationic redox polymer（PEI-Fc） and dye-linked L-proline dehydrogenase（L-proDH）.The electrochemistry of the PEI-Fc/L-proDH multilayer modified electrode was investigated by cyclic voltammetry,and the enzyme catalysis mediated by the redox polymer was studied in a solution containing L-proline.It was observed that electron communication between L-proDH and the electrode was achieved with the help of PEI-Fc.A mathematical expression for the current response was evaluated based on the Michaelis-Menten kinetics mode,and the calculated currents fitted well with the experimental data.The kinetic analysis indicates that only a small fraction of the immobilized enzyme was efficiently electrically wired by the redox polymer.

A STUDY ON SUPERCRITICAL FLUID EXTRACTION OF L-PROLINE

The extraction of L-proline from the fermentation broth filtrate with the supercritical fluid was studied. It has been proved that L-proline and most amino acids are hardly dissolved in the pure supercritical carbon dioxide fluid. When the methyl alcohol was added as an entrainer in L-proline solution or carbon dioxide fluid, the solubility of L-proline in the supercritical fluid would be greatly increased, but ethyl alcohol was unsatisfactory as an entrainer.The influences of extraction pressure, temperature, time, flow rate of fluid, concentrations of L-proline and entrainer on the yield of L-proline have been investigated for searching the optimal extraction conditions.

Direct asymmetric aldol reaction using MBHA resin-supported peptide containing L-proline unit

MBHA resin-supported tripeptide catalyst system containing L-proline unit has been developed for use in the direct asymmetric aldol reaction of acetone and aldehydes, which afford the corresponding products with satisfactory isolated yields and enantiomeric excesses. 2009 Hong Bin Zou. Published by E]sevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

PREPARATION AND EVALUATION OF HPLC BONDED PHASE WITH L-PROLINE LIGAND

This paper describes a simple method for the preparation of L-proline stationary phase bonded to silica gel and characterization of the bonded phase by IR spectrometry, elemental analysis and nitrogen adsorption method at low temperature.The enantiomeric resolutions of 3-(2-pyridyl)-3-aminopropionic acid and 2,3-diaminobutanoic acid on the bonded phase were carried out.

An Abnormal Reaction of N- (2,4-dinitrophenyl)-L-proline with Thionyl Chloride

N- (2,4-Dinitrophenyl)-4-amino-n-butyl aldehyde 3 was obtained with high yield of 80% when N- (2,4-dinitrophenyl)-L-proline 1 reacted with SOCl2 at room temperature. However, the anticipated product N- (2,4-dinitrophenyl)-tetrahydropyrrolyl-2- (4-methylthiophenyl) ketone 2 did not be produced. The mechanism was discussed in this article.

Reinvestigation of the Crystal Growth of “L-Proline Succinate” and “L-Threonine Zinc Acetate” Showing Use of Infrared Spectra for Product Identification

Reinvestigation of the growth of L-proline succinate (1) (Paramasivam and Ramachandra Raja, Journal of Crystallization Process and Technology, 2 (2012) 21 - 24;Balamurugaraj et al., Journal of Material Physics and Chemistry 1 (2013) 4 - 8) and L-threonine zinc acetate (2) (Puhal Raj and Ramachandra Raja, Photonics and Optoelectronics, 2 (2013) 56 - 64) is reported. Slow evaporation of an aqueous solution containing equimolar quantities of L-proline and succinic acid (for 1) and L-threonine and zinc acetate (for 2) results in the fractional crystallization of succinic acid (in the first case) and L-threonine (in the second case) and not any novel organic non-linear optical (NLO) crystals. In this paper, the usefulness of infrared spectra for correct product characterization is demonstrated.

L-Proline Catalyzed Solvent-Free Knoevenagel Condensation for the Synthesis of 3-Substituted Coumarins

L-Proline was utilized as an efficient organo-catalyst for the environmentally benign synthesis of 3-substituted coumarins by the Knoevenagel condensation of substituted 2-hydroxybenzaldehydes with reactive methylene compounds under solvent free conditions.

Regulatory role of L-proline in fetal pig growth and intestinal epithelial cell proliferation

L-proline(Pro)is a precursor of ornithine,which is converted into polyamines via ornithine decarboxylase(ODC).Polyamines plays a key role in the proliferation of intestinal epithelial cells.The study investigated the effect of Pro on polyamine metabolism and cell proliferation on porcine enterocytes in vivo and in vitro.Twenty-four Huanjiang mini-pigs were randomly assigned into 1 of 3 groups and fed a basal diet that contained 0.77%alanine(Ala,iso-nitrogenous control),1%Pro or 1%Pro+0.0167%α-difluoromethylornithine(DFMO)from d 15 to 70 of gestation.The fetal body weight and number of fetuses per litter were determined,and the small and large intestines were obtained on d 70±1.78 of gestation.The in vitro study was performed in intestinal porcine epithelial(IPEC-J2)cells cultured in Dulbecco’s modified Eagle medium-high glucose(DMEM-H)containing 0μmol/L Pro,400μmol/L Pro,or400μmol/L Pro+10 mmol/L DFMO for 4 d.The results showed that maternal dietary supplementation with 1%Pro increased fetal weight;the protein and DNA concentrations of the fetal small intestine;and mRNA levels for potassium voltage-gated channel,shaker-related subfamily,member 1(Kv1.1)in the fetal small and large intestines(P<0.05).Supplementing Pro to either gilts or IPEC-J2 cells increased ODC protein abundances and polyamine concentrations in the fetal intestines and IPEC-J2 cells(P<0.05).In comparison with the Pro group,the combined administration of Pro and DFMO reduced the expression of ODC protein and spermine concentration in the fetal intestine,as well as the concentrations of putrescine,spermidine and spermine in IPEC-J2 cells(P<0.05).Meanwhile,the percentage of cells in the S-phase and the mRNA levels of proto-oncogenes c-fos and c-myc were increased in response to Pro supplementation,whereas depletion of cellular polyamines with DFMO increased tumor protein p53(p53)mRNA levels(P<0.05).Taken together,dietary supplementation with Pro improved fetal pig growth and intestinal epithelial cell proliferation via enhancing polyamine synthesis.

Control of embryonic stem cell metastability by L-proline catabolism

The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,i.e.their capacity to fluctuate between different states of pluripotency,are not fully resolved.We developed and used a novel automation platform,the Cellmaker,to screen a library of metabolites on two ESC-based phenotypic assays(i.e.proliferation and colony phenotype)and identified two metabolically related amino acids,namely L-proline(L-Pro)and L-ornithine(L-Orn),as key regulators of ESC metastability.Both compounds,but mainly L-Pro,force ESCs toward a novel epiblast stem cell(EpiSC)-like state,in a dose-and time-dependent manner.Unlike EpiSCs,L-Pro-induced cells(PiCs)contribute to chimeric embryos and rely on leukemia inhibitor factor(LIF)to self-renew.Furthermore,PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF,respectively.Remarkably,PiC generation depends on both L-Pro metabolism(uptake and oxidation)and Fgf5 induction,and is strongly counteracted by antioxidants,mainly L-ascorbic acid(vitamin C,Vc).ESCs↔PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states,which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments,respectively.All together,our data provide evidence that ESC metastability can be regulated at a metabolic level.

Multicomponent synthesis of dihydropyridines catalyzed by L-proline

Multicomponent synthesis of mono and bis 4-substituted-1,4-dihydropyridines from aldehydes,dimedone and ammonium acetate in the presence of an efficient recyclable catalyst,L-proline,in high yield and short reaction time is reported.

L-proline feeding for augmented freeze tolerance of Camponotus japonicus Mayr

The successful cryopreservation of organs is a strong and widespread demand around the world but faces great challenges. The mechanisms of cold tolerance of organisms in nature inspirit researchers to find new solutions for these challenges. Especially, the thermal, mechanical, biological and biophysical changes during the regulation of freezing tolerance process should be studied and coordinated to improve the cryopreservation technique and quality of complex organs. Here the cold tolerance of the Japanese carpenter ants, Camponotus japonicus Mayr, was greatly improved by using optimal protocols and feeding on L-proline-augmented diets for 5 days. When cooling to -27.66 ℃, the survival rate of frozen ants increased from 37.50% ± 1.73% to 83.88% ± 3.67%. Profiling of metabolites identified the concentration of whole-body L-proline of ants increased from 1.78 to 4.64 ng g-1 after 5-day feeding. High Lproline level, together with a low rate of osmotically active water and osmotically inactive water facilitated the prevention of cryoinjury. More importantly, gene analysis showed that the expression of ribosome genes was significantly up-regulated and played an important role in manipulating freezing tolerance. To the best of our knowledge, this is the first study to link genetic variation to the enhancement of ants’ cold tolerance by feeding exogenous cryoprotective compound. It is worth noting that the findings provide the theoretical and technical foundation for the cryopreservation of more complex tissues,organs, and living organisms.

L-Proline catalyzed aldol reactions between acetone and aldehydes in supercritical fluids:An environmentally friendly reaction procedure

The direct asymmetric aldol reaction between various aldehydes and acetone catalyzed by L-proline catalyst was successfully carried out in supercritical CO_(2) (scCO_(2)) and 1,1,1,2-tetrafluoroethane (R-134a) fluids.The enantioselectivity of 84% ee to the targeted product was achieved under 20 MPa,40 °C,and 15 mol% of the catalyst in supercritical CO_(2) (scCO_(2)) fluid.The effects of reaction parameters,such as temperature,pressure,catalyst loading and different substituted aldehydes on both enantioselectivity and aldol yield were discussed.The titled reaction was also performed in 1,1,1,2-tetrafluoroethane,and the obtained results were compared with those in scCO2.This new reaction procedure provides an environmental asymmetric aldol reaction system as compared with that in organic solvents.

Synthesis of chiral spirocyclo-quaternary ammonium salts from L-proline and their application as phase-transfer catalysts in asymmetric alkylation

A new series of chiral phase-transfer catalysts 7a-7h were designed and synthesized from L-proline with moderate to good yields.＇The catalytic activity of 7a-Th for the asymmetric alkylation of glycine Schiff bases was evaluated, and some interesting relationships between structure and catalytic activity were revealed.

L-Proline catalyzed one-pot multi-component synthesis of 2-(1,3-diphenyl-1H-pyrazol-4-yl)quinazolin-4(3H)-one derivatives and their biological studies

A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an L-proline catalyzed one-pot multi-component reaction approach.All the synthesized compounds were characterized and screened for their antimicrobial,antifungal and anti-tubercular activities.

An Improved Practical Route to （±）-Epibatidine through L-Proline Catalyzed Intramolecular Michael Addition

This paper describes a rapid and practical synthetic route involving six-step reactions towards the diastereose- lectively synthesis of （±）-endo-Epibatidine, starting from 6-chloro-3-pyridinecarboxaldehye. The effective Henry reaction gave precursor （E）-6-（6-chloropyridin-3-yl）-5-nitrohex-5-en-2-one （3a） which could be used in the next step. Various benzoic acid derivatives were used to optimize intramolecular Michael addition of ketone to pyridinylnitroolefins to provide the key intermediate 3-（6-chloropyridin-3-yl）-4-nitrocyclohexanone （±）-7a） with high yield.