Photorelease of amino acid neurotransmitters from pyrenylmethyl ester conjugates

The linkage of model neurotransmitter l-amino acids, such as glycine, alanine, β-alanine, glutamic acid and γ-aminobutyric acid, to a pyrenylmethyl group as the fluorescent moiety through an ester bond at their carboxylic functions at the main and side chains (in the case of glutamic acid) was investigated. The behaviour of the resulting fluorescent conjugates towards photocleavage was studied in different cleavage conditions, namely the wavelength of irradiation and the use of different solvents, in a photochemical reactor equipped with lamps of 254, 300, 350 and 419 nm, followed by HPLC/UV monitoring.     

位点特异、拓扑结构明确的蛋白质-聚氨基酸偶联物的简洁合成

发展位点特异且具有明确拓扑结构的蛋白质-高分子偶联物是高分子和化学生物学领域共同面对的挑战之一.在聚合物末端精确引入一个或多个具有特殊反应活性的生物正交官能团是实现位点特异生物偶联的关键前提.这一过程通常比较低效、需要多步骤的官能团转化、聚合后修饰以及保护脱保护,费时且繁琐.最近,通过在聚合过程中原位生成官能团,以一锅-两步的过程得到可直接用于蛋白质偶联的异遥爪聚合物,从而实现了多种不同拓扑结构的蛋白质-聚氨基酸偶联物的快速构筑.这一简洁的合成路线实现了以前尚未获得的头-尾相接的环状偶联物的制备,使这些偶联物表现出了很强的体外酶稳定性以及热稳定性.该工作是蛋白质-高分子偶联化学的一次创新的尝试;同时,利用该方法所制备的偶联物在蛋白质药物领域具有广阔的应用前景.     

Bacteriostatic activities of N-substituted tris-thioureas bearing amino acid and aniline substituents

A series of tri-substituted thiourea derivatives were synthesized by the reaction of 1,3,5-triacetylbenzoyl isothiocyanate with aminoacids and aniline derivatives. All thiourea derivatives were characterized by FT-IR, ¹H and ¹³C NMR spectroscopy. Antibacterial activities against wild-type Escherichia coli American Type Culture Collection 8739 were determined by use of the turbidimetric methodto evaluate the effect of varying amino groups on the synthesized thioureas. Tris-thiourea derivatives bearing ortho-chloroaryl substituents showed excellent antibacterial activity against E. coli with minimal inhibitory concentration (MIC) of 96 ppm. The optimum inhibition was dependent on the type of amines and the position of the halogen in aniline.     

Preparation of synthetic auxin-amino acid conjugates

Auxin amide conjugates are regulators of the most important auxin, indole-3-acetic acid (IAA), which is considered responsible for many important processes within the plants. Herein, amide conjugates of IAA were synthesized employing a simple and efficient coupling method with WSCI·HCl, a water-soluble condensing reagent, in the presence of 1-hydroxybenzotriazole. IAA conjugates with 10 amino acids along with their corresponding methyl esters were prepared in excellent yields, up to 95%, aiming to facilitate their identification in plant species. Eight IAA-amino acid methyl ester conjugates are characterized here for the first time.     

In silico prediction of deleterious single amino acid polymorphisms from amino acid sequence

Molecular cause of human disease retains as one of the most attractive scientific research targets for decades. An effective approach toward this topic is analysis and identification of disease-related amino acid polymorphisms. In this work, we developed a concise and promising deleterious amino acid polymorphism identification method SeqSubPred based on 44 features solely extracted from protein sequence. SeqSubPred achieved surprisingly good predictive ability with accuracy (0.88) and area under receiver operating characteristic (0.94) without resorting to homology or evolution information, which is frequently used in similar methods and usually more complex and time-consuming. SeqSubPred also identified several critical sequence features obtained from random forests model, and these features brought some interesting insights into the factors affecting human disease-related amino acid substitutions. The online version of SeqSubPred method is available at montana.informatics.indiana.edu/cgi-bin/seqmut/seqsubpred.cgi     

Liquid chromatography of jasmonic acid amine conjugates

Summary Racemic jasmonic acid (3R,7R/3S,7S)-(±)-JA) was chemically conjugated with different biogenic amines originating from aliphatic and aromatic α-amino acids by decarboxylation. The resulting isomeric compounds were subjected to reversed-phase high-performance liquid chromatography (HPLC) and to HPLC on the chiral stationary phases Chiralpak AS and Nucleodex β-PM. Under reversed-phase conditions, all the homologous amine derivatives tested could be separated from each other except the JA-conjugates containing 2-phenyl-ethylamine and 3-methylbutylamine. On both chiral supports the (3R,7R)-(−)-JA conjugates eluted earlier than those of the enantiomeric counterpart (3S,7S)-(+)-JA. On Chiralpak AS all the isomers studied could be separated to baseline with a mobile phase containingn-hexane and 2-propanol. The calculated resolution factors were between 1.80 and 4.17. The pairs of isomers were also chromatographed on the cyclodextrin stationary phase Nucleodex β-PM with methanol-triethylammonium acetate buffer as mobile phase. Under these conditions resolution factors were between 0.74 and 1.29. The individual isomers were chiroptically characterized by measurement of their circular dichroism.     

Chiral separation of amide conjugates of jasmonic acid by liquid chromatography

Summary Synthetic amide conjugates of (−)-jasmonic acid and its (+)-enantiomer were resolved by means of chiral liquid chromatography. The diastereomeric pairs prepared by chemical reaction of (±)-jasmonic acid with a series of (S)- or (R)-amino acids and with some (S)-amino acid alcohols were completely separated on Chiralpak AS using a mixture of n-hexane/2-propanal as mobile phase. The retention data indicate that the (−)-jasmonic acid conjugates eluted faster than those of the (+)-enantiomer, independent on the configuration of the bound amino acid. Likewise, enantiomeric derivatives of (±)-jasmonic acid and non-chiral amino acids were completely separated on the chiral stationary phase and showed the same elution sequence. The resolution factors,Rs, were found to range between 1.13 and 6.64. The separated compounds were chiropatically analyzed by measurement of the circular dichroism. Presented at the 21^st ISC held in Stuttgart, Germany, 15^th–20^th September, 1996     

PreSSAPro: a software for the prediction of secondary structure by amino acid properties

PreSSAPro is a software, available to the scientific community as a free web service designed to provide predictions of secondary structures starting from the amino acid sequence of a given protein. Predictions are based on our recently published work on the amino acid propensities for secondary structures in either large but not homogeneous protein data sets, as well as in smaller but homogeneous data sets corresponding to protein structural classes, i.e. all-alpha, all-beta, or alpha–beta proteins. Predictions result improved by the use of propensities evaluated for the right protein class. PreSSAPro predicts the secondary structure according to the right protein class, if known, or gives a multiple prediction with reference to the different structural classes. The comparison of these predictions represents a novel tool to evaluate what sequence regions can assume different secondary structures depending on the structural class assignment, in the perspective of identifying proteins able to fold in different conformations. The service is available at the URL http://bioinformatica.isa.cnr.it/PRESSAPRO/.     

Distance dependency and minimum amino acid alphabets for decoy scoring potentials

The validity and accuracy of a proposed tertiary structure of a protein can be assessed in several ways. Scoring such a structure by a knowledge‐based potential is a well‐known approach in molecular biophysics, an important task in structure prediction and refinement, and a key step in several experiments on protein structures. Although several parameterizations for such models have been derived over the course of time, improvements in accuracy by explicitly using continuous distance information have not been suggested yet. We close this methodological gap by formulating the parameterization of a protein structure model as a linear program. Optimization of the parameters was performed using amino acid distances calculated for the residues in topology rich 2830 protein structures. We show the capability of our derived model to discriminate between native structures and decoys for a diverse set of proteins. In addition, we discuss the effect of reduced amino acid alphabets on the model. In contrast to studies focusing on binary contact schemes (without considering distance dependencies and proposing five symbols as optimal alphabet size), we find an accurate protein alphabet size to contain at least five symbols, preferably more, to assure a satisfactory fold recognition capability. © 2012 Wiley Periodicals, Inc.     

A compilation of amino acid analyses of proteins

The amino acid analyses of 183 proteins, as residues per 1000 residues, are given. In addition the carbohydrate content and the content of any noncommon amino acids are also given. The sources of all proteins are presented.     

Isosteviol‐amino Acid Conjugates as Highly Efficient Organocatalysts for the Asymmetric One‐pot Three‐component Mannich Reactions

Isosteviol‐amino acid conjugates were synthesized and used as chiral catalysts for the asymmetric three‐component Mannich reaction with hydroxyacetone as donor molecule. Good yields (up to 98%) and excellent stereoselectivities (up to 97:3 dr and 99% ee) were achieved in a short reaction time. In addition, syn‐ or anti‐configurations of α‐hydroxy‐β‐amino carbonyl compounds were obtained as main products with different chiral catalysts.     

Synthesis and antitumour activity of arctigenin amino acid ester derivatives against H22 hepatocellular carcinoma

Arctigenin (ARG) is famous in its abundant pharmacological activity. However, many researches in it entered the bottleneck period because of its poor water solubility. The derivatives of ARG have been synthesised with five amino acids which have t-Butyloxy carbonyl (BOC) as a protective group. We examined the effects of removing BOC. The results showed that the amino acid derivatives without protective group have better water solubility and nitrite-clearing ability than ARG. Based on these results, ARG6′ and ARG9′ were selected at a dosage of 40 mg/kg to evaluate their antitumour activity. The percentage inhibition rate of ARG6′ and ARG9′ were 55.87 and 51.40, respectively, which was twice as much as ARG. Furthermore, they could increase liver and kidney indexes and produce less damage in these organs. In brief, this study provides a basis for new drug development.     

A new ureido-substituted amino acid from the tubers of Gymnadenia conopsea

A new ureido-substituted amino acid, conopsamide A (1), has been isolated from an ethanolic extract of the tubers of Gymnadenia conopsea. Its structure was elucidated by extensive spectroscopic analysis, and the absolute configuration was assigned by Marfey's method. The new compound was evaluated for in vitro assay for HDAC1 (Histone Deacetylase 1) inhibitory activity.     

Synthesis,structural characterization and cytotoxic activity of diorganotin(IV) complexes of N‐(5‐halosalicylidene)‐α‐amino acid

Fourteen new diorganotin(IV) complexes of N‐(5‐halosalicylidene)‐α‐amino acid, R′₂Sn(5‐X‐2‐OC₆H₃CH?NCHRCOO) (where X = Cl, Br; R = H, Me, i‐Pr; R′ = n‐Bu, Ph, Cy), were synthesized by the reactions of diorganotin halides with potassium salt of N‐(5‐halosalicylidene)‐α‐amino acid and characterized by elemental analysis, IR and NMR (¹H, ¹³C and ¹¹⁹Sn) spectra. The crystal structures of Bu₂Sn(5‐Cl‐2‐OC₆H₃CH?NCH(i‐Pr)COO) and Ph₂Sn(5‐Br‐2‐OC₆H₃CH?NCH(i‐Pr)COO) were determined by X‐ray single‐crystal diffraction and showed that the tin atoms are in a distorted trigonal bipyramidal geometry and form five‐ and six‐membered chelate rings with the tridentate ligand. Bioassay results of a few compounds indicated that the compounds have strong cytotoxic activity against three human tumour cell lines, i.e. HeLa, CoLo205 and MCF‐7, and the activity decreased in the order Cy>n‐Bu>Ph for the R′ group bound to tin. Copyright © 2005 John Wiley & Sons, Ltd.     

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.     

Synthesis and copolymerization of oligo(lactic acid) derived norbornene macromonomers with amino acid derived norbornene monomer: Formation of the 3D macroporous scaffold

Norbornene macromonomers 2 and 3 bearing 10‐ and 20‐mers of lactide were synthesized by ring‐opening polymerization of lactide using 5‐norbornene‐2, 3‐exo‐exo‐dimethanol as an initiator and DBU as a catalyst. Macromonomers 2 and 3 were copolymerized with amino acid derived norbornene monomer 1 , using the Grubbs 2nd generation ruthenium catalyst. The random and block copolymers with M_n's ranging from 28,000 to 180,000 were obtained almost quantitatively where the M_n's of the block copolymers were higher than those of the random ones. Three‐dimensional macroporous structure polymers with average pore size of 10 µm could be found in poly( 1 ) and the block co‐polymer of 1 and 2 or 1 and 3 at the high ratio of 1 . Meanwhile, poly( 2 ) and poly( 3 ) along with block and random copolymers with low ratio of 1 exhibit much larger pores in the range of 50–300 µm. The porosity increased with increase in the unit ratio of 1 . The compressive strength of the porous structure of poly( 2 ) and poly( 3 ) was improved by the copolymerization with 1 . © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1660–1670     

Synthesis and specific biodegradation of novel polyesteramides containing amino acid residues

Novel polyesteramides were synthesized from p‐nitrophenyl esters of sebacic or adipic acids and diamines containing α‐amino acid ester groups. The optimal polymerization condition was 60 °C in N,N‐dimethylformamide. The structures of these polymers were confirmed by IR and NMR. The number‐average molecular weights of these polyesteramides ranged from 2280 to 23,600 (except for the polymers containing glycine residues), depending on the nature of the amino acid used. The biodegradability of the polyesteramides was investigated by in vitro hydrolysis with proteases and a lipase as catalysts in borate buffer solutions. The results indicated that the polymers containing L ‐phenylalanine were hydrolyzed most effectively by α‐chymotrypsin, subtilisin Carlsberg, and subtilisin BPN′. The polyesteramides containing other amino acid residues also underwent hydrolysis to different extents, reflecting the substrate specificity of the proteases. Lipase had almost no effect on the hydrolytic degradation of these polyesteramides. The polymers containing glycine residues were hardly decomposed by any of the enzymes used. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1318–1328, 2001     

Simultaneous separation of jasmonic acid conjugates with amino acids by MEKC

Jasmonic acid (JA) conjugates with amino acids (AAs) are a group of plant hormone in the family of jasmonates. The separation of stereoisomers of JA‐AA conjugates is a very challenging work since these stereoisomers have similar chromatographic and electrophoretic behavior. Simultaneous separation of ten (±)‐JA conjugates with five AAs including l‐ Tyr (tyrosine), l‐ leucine, l‐ Ile (isoleucine), l‐ valine, and l‐ phenylalanine and their stereoisomers has been achieved by MEKC with diode array detector in this work. Optimum separation of the analytes was obtained on a 61.5 cm × 75 μm id capillary using a running buffer containing 80 mM SDS and 50 mM phosphates (pH 7.0) at +18 kV applied voltage and capillary temperature of 35°C. Ten stereoisomers of JA conjugates with five AAs are completely separated in 13 min. The RSDs of the migration times and peak areas of the ten stereoisomers were in the range of 0.48–1.03% and 1.03–2.07%, respectively. In the tested concentration range, good linear relationships (correlation coefficients above 99%) between peak areas and concentrations of the analytes were observed. The proposed method has been successfully applied to the analysis of spiked rice floret sample and original reaction solution of (±)‐JA‐Ile conjugate and (±)‐JA‐Tyr conjugate. The recoveries ranged from 91.7 to 107.6% for the rice floret sample and 92.9 to 107.2% for the original reaction solution.