The Synthesis of a Cubane-Substituted Dipeptide

2012 ◽  
Vol 65 (6) ◽  
pp. 690 ◽  
Author(s):  
Quentin I. Churches ◽  
Roger J. Mulder ◽  
Jonathan M. White ◽  
John Tsanaktsidis ◽  
Peter J. Duggan
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
High Sensitivity ◽  
Pure Form ◽  
Bioactive Molecules ◽  
Side Chains ◽  
Cyclic Hydrocarbon ◽  
Wide Range ◽  
Effective Synthesis ◽  
Dipeptide Derivative

Amino acids and peptides bearing cyclic hydrocarbon side-chains are of interest in the development of a wide range of bioactive molecules. The preparation of an amino acid and a dipeptide derivative bearing an unfunctionalised cubane substituent is described. Attempts to prepare a cubylalanine derivative via the corresponding dehydroalanine were unsuccessful due to the high sensitivity of this vinyl cubane compound. Conversely, the addition of cubyllithium to a (RS)-glyoxylate sulfinimine led to an effective synthesis of a cubylglycine derivative and a cubane-substituted dipeptide in diastereomerically pure form.

scholarly journals Making Sense of “Nonsense” and More: Challenges and Opportunities in the Genetic Code Expansion, in the World of tRNA Modifications

2022 ◽  
Vol 23 (2) ◽  
pp. 938
Author(s):  
Olubodun Michael Lateef ◽  
Michael Olawale Akintubosun ◽  
Olamide Tosin Olaoba ◽  
Sunday Ocholi Samson ◽  
Malgorzata Adamczyk
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
Protein Design ◽  
Side Chains ◽  
Vast Number ◽  
Trna Modifications ◽  
Wide Range ◽  
Challenges And Opportunities ◽  
Code Extension ◽  
Genetic Code Expansion

The evolutional development of the RNA translation process that leads to protein synthesis based on naturally occurring amino acids has its continuation via synthetic biology, the so-called rational bioengineering. Genetic code expansion (GCE) explores beyond the natural translational processes to further enhance the structural properties and augment the functionality of a wide range of proteins. Prokaryotic and eukaryotic ribosomal machinery have been proven to accept engineered tRNAs from orthogonal organisms to efficiently incorporate noncanonical amino acids (ncAAs) with rationally designed side chains. These side chains can be reactive or functional groups, which can be extensively utilized in biochemical, biophysical, and cellular studies. Genetic code extension offers the contingency of introducing more than one ncAA into protein through frameshift suppression, multi-site-specific incorporation of ncAAs, thereby increasing the vast number of possible applications. However, different mediating factors reduce the yield and efficiency of ncAA incorporation into synthetic proteins. In this review, we comment on the recent advancements in genetic code expansion to signify the relevance of systems biology in improving ncAA incorporation efficiency. We discuss the emerging impact of tRNA modifications and metabolism in protein design. We also provide examples of the latest successful accomplishments in synthetic protein therapeutics and show how codon expansion has been employed in various scientific and biotechnological applications.

scholarly journals Analysis of Htra Gene from Zebrafish (Danio Rerio)

2015 ◽  
Vol 10 (2) ◽  
Author(s):  
M. Murwantoko ◽  
Chio Oka ◽  
Masashi Kawaichi
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Danio Rerio ◽  
Serine Proteases ◽  
Catalytic Domain ◽  
Fruit Fly ◽  
Wide Range ◽  
Igf Binding ◽  
Bacterial Homolog

HtrA which is characterized by the combination of a trypsin-like catalytic domain with at least one C-terminalPDZ domain is a highly conserved family of serine proteases found in a wide range of organisms. However theidentified HtrA family numbers varies among spesies, for example the number of mammalian, Eschericia coli,fruit fly-HtrA family are 4, 3 and 1 gene respectively. One gene is predicted exist in zebrafish. Since no completeinformation available on zebrafish HtrA, in this paper zebrafish HtrA (zHtrA) gene was analyzed. The zHtrA isbelonged to HtrA1 member and predicted encodes 478 amino acids with a signal peptide, a IGF binding domain,a Kazal-type inhibitor domain in the up stream of HtrA-bacterial homolog. At the amino acid sequence the zHtrA1showed the 69%, 69%, 68%, 54% and 54% with the rat HtrA1, mouse HtrA1, human HtrA1, human HtrA3 andmouse HtrA4 respectively. The zHtrA1 is firstly expressed at 60 hpf and mainly in the vertebral rudiments in thetail region.

Structural characterization of folded and extended conformations in peptides containing γ amino acids with proteinogenic side chains: crystal structures of γn, (αγ)n and γγδγ sequences

2015 ◽  
Vol 39 (5) ◽  
pp. 3319-3326 ◽  
Author(s):  
Madhusudana M. B. Reddy ◽  
K. Basuroy ◽  
S. Chandrappa ◽  
B. Dinesh ◽  
B. Vasantha ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Crystal Structures ◽  
Structural Characterization ◽  
Side Chains ◽  
Amino Acid Residues

γn amino acid residues can be incorporated into structures in γn and hybrid sequences containing folded and extended α and δ residues.

An Automated Detection System for Most L-α-Amino Acids

1969 ◽  
Vol 15 (2) ◽  
pp. 154-161 ◽  
Author(s):  
K Van Dyke ◽  
C Szustkiewicz
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Detection System ◽  
Automated System ◽  
Acid Oxidase ◽  
Enzymatic Reactions ◽  
Amino Acid Oxidase ◽  
Automated Method ◽  
Wide Range

Abstract An automated system for the determination of the L-α form of the majority of amino acids is presented. The method is based upon oxidative deamination of the amino acid coupled with oxidation of o-dianisidine by hydrogen peroxide. This procedure can be used comparatively for the determination of a mixture of L-α-amino acids or for the majority of separated L-α-amino acids (especially in conjunction with column separations from urine and blood which give falsely positive identification with ninhydrin detection). The stereospecific nature of the L-α-amino acid oxidase enables the investigator to quantitate the amount of L-α-amino acid in the presence of the D-α form. From an academic viewpoint, the extreme sensitivity and wide range of the detection system make it advantageous for the study of the enzyme itself. This automated method also may be employed to follow enzymatic reactions—e.g., those catalyzed by peptidases or racemases. The methodology is extremely convenient with good reagent stability and is much more sensitive than manometric technics.

scholarly journals Probiotic Administration Increases Amino Acid Absorption from Plant Protein: a Placebo-Controlled, Randomized, Double-Blind, Multicenter, Crossover Study

2020 ◽  
Vol 12 (4) ◽  
pp. 1330-1339 ◽  
Author(s):  
Ralf Jäger ◽  
Javier Zaragoza ◽  
Martin Purpura ◽  
Stefania Iametti ◽  
Mauro Marengo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Content ◽  
Bioactive Molecules ◽  
Plant Proteins ◽  
Probiotic Supplementation ◽  
Double Blind ◽  
Pea Protein ◽  
Acid Absorption ◽  
Amino Acid Absorption

Abstract The fate of dietary protein in the gut is determined by microbial and host digestion and utilization. Fermentation of proteins generates bioactive molecules that have wide-ranging health effects on the host. The type of protein can affect amino acid absorption, with animal proteins generally being more efficiently absorbed compared with plant proteins. In contrast to animal proteins, most plant proteins, such as pea protein, are incomplete proteins. Pea protein is low in methionine and contains lower amounts of branched-chain amino acids (BCAAs), which play a crucial role in muscle health. We hypothesized that probiotic supplementation results in favorable changes in the gut microbiota, aiding the absorption of amino acids from plant proteins by the host. Fifteen physically active men (24.2 ± 5.0 years; 85.3 ± 12.9 kg; 178.0 ± 7.6 cm; 16.7 ± 5.8% body fat) co-ingested 20 g of pea protein with either AminoAlta™, a multi-strain probiotic (5 billion CFU L. paracasei LP-DG® (CNCM I-1572) plus 5 billion CFU L. paracasei LPC-S01 (DSM 26760), SOFAR S.p.A., Italy) or a placebo for 2 weeks in a randomized, double-blind, crossover design, separated by a 4-week washout period. Blood samples were taken at baseline and at 30-, 60-, 120-, and 180-min post-ingestion and analyzed for amino acid content. Probiotic administration significantly increased methionine, histidine, valine, leucine, isoleucine, tyrosine, total BCAA, and total EAA maximum concentrations (Cmax) and AUC without significantly changing the time to reach maximum concentrations. Probiotic supplementation can be an important nutritional strategy to improve post-prandial changes in blood amino acids and to overcome compositional shortcomings of plant proteins. ClinicalTrials.gov Identifier: ISRCTN38903788

Effect of thenardite on the direct detection of aromatic amino acids: implications for the search for life in the solar system

2009 ◽  
Vol 8 (4) ◽  
pp. 291-300 ◽  
Author(s):  
C. Doc Richardson ◽  
Nancy W. Hinman ◽  
Jill R. Scott
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Amino Acid ◽  
Aromatic Amino Acids ◽  
Laser Desorption ◽  
Ionization Mechanism ◽  
Side Chains ◽  
Ion Cyclotron Resonance ◽  
Laser Desorption Mass Spectrometry ◽  
Aromatic Side Chains

AbstractWith the discovery of Na-sulphate minerals on Mars and Europa, recent studies using these minerals have focused on their ability to assist in the detection of bio/organic signatures. This study further investigates the ability of thenardite (Na2SO4) to effectively facilitate the ionization and identification of aromatic amino acids (phenylalanine, tyrosine and tryptophan) using a technique called geomatrix-assisted laser desorption/ionization in conjunction with a Fourier transform ion cyclotron resonance mass spectrometry. This technique is based on the ability of a mineral host to facilitate desorption and ionization of bio/organic molecules for detection. Spectra obtained from each aromatic amino acid alone and in combination with thenardite show differences in ionization mechanism and fragmentation patterns. These differences are due to chemical and structural differences between the aromatic side chains of their respective amino acid. Tyrosine and tryptophan when combined with thenardite were observed to undergo cation-attachment ([M+Na]+), due to the high alkali ion affinity of their aromatic side chains. In addition, substitution of the carboxyl group hydrogen by sodium led to formation of [M-H+Na]Na+ peaks. In contrast, phenylalanine mixed with thenardite showed no evidence of Na+ attachment. Understanding how co-deposition of amino acids with thenardite can affect the observed mass spectra is important for future exploration missions that are likely to use laser desorption mass spectrometry to search for bio/organic compounds in extraterrestrial environments.

scholarly journals Electrophysiological evidence for acidic, basic, and neutral amino acid olfactory receptor sites in the catfish.

1984 ◽  
Vol 84 (3) ◽  
pp. 403-422 ◽  
Author(s):  
J Caprio ◽  
R P Byrd
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ictalurus Punctatus ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Receptor Potential ◽  
Side Chains ◽  
Short Side ◽  
Neutral Amino Acids ◽  
Receptor Sites

Electrophysiological experiments indicate that olfactory receptors of the channel catfish, Ictalurus punctatus, contain different receptor sites for the acidic (A), basic (B), and neutral amino acids; further, at least two partially interacting neutral sites exist, one for the hydrophilic neutral amino acids containing short side chains (SCN), and the second for the hydrophobic amino acids containing long side chains (LCN). The extent of cross-adaptation was determined by comparing the electro-olfactogram (EOG) responses to 20 "test" amino acids during continuous bathing of the olfactory mucosa with water only (control) to those during each of the eight "adapting" amino acid regimes. Both the adapting and test amino acids were adjusted in concentrations to provide approximately equal response magnitudes in the unadapted state. Under all eight adapting regimes, the test EOG responses were reduced from those obtained in the unadapted state, but substantial quantitative differences resulted, depending upon the molecular structure of the adapting stimulus. Analyses of the patterns of EOG responses to the test stimuli identified and characterized the respective "transduction processes," a term used to describe membrane events initiated by a particular subset of amino acid stimuli that are intricately linked to the origin of the olfactory receptor potential. Only when the stimulus compounds interact with different transduction processes are the stimuli assumed to bind to different membrane "sites." Four relatively independent L-alpha-amino acid transduction processes (and thus at least four binding sites) identified in this report include: (a) the A process for aspartic and glutamic acids; (b) the B process for arginine and lysine; (c) the SCN process for glycine, alanine, serine, glutamine, and possibly cysteine; (d) the LCN process for methionine, ethionine, valine, norvaline, leucine, norleucine, glutamic acid-gamma-methyl ester, histidine, phenylalanine, and also possibly cysteine. The specificities of these olfactory transduction processes in the catfish are similar to those for the biochemically determined receptor sites for amino acids in other species of fishes and to amino acid transport specificities in tissues of a variety of organisms.

The relationships between the concentrations of individual amino acids and protein in wheat and barley grain grown at selected locations throughout Manitoba

1996 ◽  
Vol 76 (2) ◽  
pp. 163-169 ◽  
Author(s):  
R. J. Boila ◽  
S. C. Stothers ◽  
L. D. Campbell
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Barley Grain ◽  
Regression Equations ◽  
Acid Protein ◽  
Wide Range ◽  
Indispensable Amino Acids ◽  
Protein Amino Acids ◽  
Barley Protein ◽  
Amino Acid Concentrations

The concentrations of protein and individual amino acids were determined in the grain from three cultivars of wheat and three cultivars of barley, each grown at 12 locations throughout Manitoba over 3 consecutive years. Protein concentration differed (P < 0.05) among the cultivars of wheat but not (P > 0.05) among cultivars of barley. Although the concentrations of several amino acids differed (P < 0.05) among cultivars of wheat or barley the differences among cultivars of each grain were not considered to be critical in relation to the requirements for indispensable amino acids for swine or poultry. The percentage of an ammo acid in the DM of wheat and barley increased (P < 0.05) linearly with an increase in percentage of protein in the grain. The wide range of r2 (0.29 to 0.88) obtained for this amino acid-protein relationship may be due to the different effect of environment (location and year of growth) on the concentration of individual amino acids, compared to protein, among cultivars of wheat or barley. The percentage of total variance due to an interaction between cultivar and environment was low for protein but was several fold higher for individual amino acids. The error in the prediction of amino acid concentrations with regression equations may be no different than the error associated with predicting the mean concentrations of amino acids in the protein of wheat or barley as g (100 g protein)−1, and obtained from tabulations of analyses. However, regression equations for lysine in wheat and barley did account for the significant (P < 0.05) decrease in concentration of lysine in the protein as the percentage of protein in these grains increased. Key words: Grain, wheat, barley, protein, amino acids, Manitoba

Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine

1987 ◽  
Vol 58 (2) ◽  
pp. 251-266 ◽  
Author(s):  
J. F. MacDonald ◽  
Z. Miljkovic ◽  
P. Pennefather
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Aspartic Acid ◽  
Excitatory Amino Acids ◽  
Hippocampal Neurons ◽  
Excitatory Amino Acid ◽  
Outward Current ◽  
Bathing Solution ◽  
Wide Range ◽  
Repeated Applications

1. Mouse hippocampal neurons grown in dissociated cell culture were patch clamped using a whole cell voltage clamp (discontinuous switching clamp) technique. The currents generated by pressure applications of excitatory amino acids were studied over a wide range of holding potentials, and current-voltage curves were plotted. Excitatory amino acids that activated the N-methyl-D-aspartic acid (NMDA) receptor demonstrated some degree of desensitization with repeated applications, whereas the currents observed in response to kainic acid (KAI) did not. Desensitization could be minimized by keeping the frequency of application sufficiently low (i.e., less than 0.1 Hz). 2. The short-acting dissociative anaesthetic, ketamine (2–50 microM), selectively blocked L-aspartic acid (L-Asp), NMDA, and L-glutamic acid (L-Glu) currents while sparing those in response to KAI. Therefore, ketamine is a relatively selective blocker of the NMDA response versus that (those) activated by KAI. 3. The block by ketamine of excitatory amino acid currents is highly voltage dependent. Concentrations of ketamine that had little effect on outward current responses at depolarized potentials were quite effective at blocking inward current responses at hyperpolarized potentials. In contrast, DL-2-amino-5-phosphonovaleric acid (APV) was equally effective at blocking both inward and outward currents (voltage independent). The voltage dependence of ketamine (a positively charged molecule) could be accounted for if ketamine blocked the NMDA response by binding to a site that experienced 55% of the membrane field. 4. In the presence of ketamine, peak inward currents evoked by repeated applications of NMDA, L-Asp, or L-Glu progressively declined to a steady-state level of block (use-dependent block). This decrement occurred at frequencies much lower than those that were employed to demonstrate desensitization (in the absence of ketamine). Moving the membrane potential to depolarized values did not, in itself, relieve the ketamine block. However, if the appropriate excitatory amino acid (L-Asp, NMDA, L-Glu) was applied during the period of depolarization, a relief of the block could be demonstrated. No recovery from the blockade occurred with periods of rest (no amino acid application) as long as 5 min. Furthermore, no recovery was observed even when ketamine was washed out of the bathing solution until the appropriate agonist was applied. Thus recovery from blockade, like development of blockade, was use dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Sign in / Sign up

Export Citation Format

Share Document