3506-25-0Relevant articles and documents
Glutamates 78 and 122 in the Active Site of Saccharopine Dehydrogenase Contribute to Reactant Binding and Modulate the Basicity of the Acid-Base Catalysts
Ekanayake, Devi K.,Andi, Babak,Bobyk, Kostyantyn D.,West, Ann H.,Cook, Paul F.
, p. 20756 - 20768 (2010)
Saccharopine dehydrogenase catalyzes the NAD-dependent oxidative deamination of saccharopine to give L-lysine and α-ketoglutarate. There are a number of conserved hydrophilic, ionizable residues in the active site, all of which must be important to the overall reaction. In an attempt to determine the contribution to binding and rate enhancement of each of the residues in the active site, mutations at each residue are being made, and double mutants are being made to estimate the interrelationship between residues. Here, we report the effects of mutations of active site glutamate residues, Glu78 and Glu122, on reactant binding and catalysis. Site-directed mutagenesis was used to generate E78Q, E122Q, E78Q/E122Q, E78A, E122A, and E78A/E122A mutant enzymes. Mutation of these residues increases the positive charge of the active site and is expected to affect the pKa values of the catalytic groups. Each mutant enzyme was completely characterized with respect to its kinetic and chemical mechanism. The kinetic mechanism remains the same as that of wild type enzymes for all of the mutant enzymes, with the exception of E78A, which exhibits binding of α-ketoglutarate to E and E·NADH. Large changes in V/K Lys, but not V, suggest that Glu78 and Glu122 contribute binding energy for lysine. Shifts of more than a pH unit to higher and lower pH of the pKa values observed in the V/KLys pH-rate profile of the mutant enzymes suggests that the presence of Glu78 and Glu122 modulates the basicity of the catalytic groups.
4-Methoxy-2,3-6-trimethylbenzenesulphonyl (Mtr): a New Aminoprotecting Group in Peptide Synthesis
Fujino, Masahiko,Wakimasu, Mitsuhiro,Kitada, Chieko
, p. 445 - 446 (1982)
The 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr) group used to protect the ε-amino function of lysine can be readily removed with 0.15-0.3 M methanesulphonic acid in trifluoroacetic acid - thioanisole (9:1) but is completely resistant to hydrogenolysis or treatment with neat trifluoroacetic acid and hydrogen chloride, and thus can be used in the solution synthesis of methionine-containing peptides, such as mastoparan X and chicken gastrin releasing peptide (c-GRP).
Synthesis of monolysyl advanced glycation endproducts and their incorporation into collagen model peptides
Woods, Tom M.,Kamalov, Meder,Harris, Paul W. R.,Cooper, Garth J. S.,Brimble, Margaret
, p. 5740 - 5743 (2012)
The synthesis of advanced glycation endproducts (AGEs), CML, CEL, and pyrraline and their incorporation into collagen model peptides is reported. AGEs are modified amino acids that form on proteins such as collagen and are thought to play a significant role in the pathogenesis of many diseases, particularly diabetes. The synthesis and incorporation of these compounds into synthetic peptides is a key step in developing model systems with which to investigate AGE-modified proteins.
Thalassosamide, a Siderophore Discovered from the Marine-Derived Bacterium Thalassospira profundimaris
Zhang, Fan,Barns, Kenneth,Hoffmann, F. Michael,Braun, Doug R.,Andes, David R.,Bugni, Tim S.
, p. 2551 - 2555 (2017)
Here we describe the rapid identification and prioritization of novel active marine natural products using an improved dereplication strategy. During the course of our screening of marine natural product libraries, a new cyclic trihydroxamate compound, thalassosamide, was discovered from the α-proteobacterium Thalassospira profundimaris. Its structure was determined by 2D NMR and MS/MS experiments, and the absolute configuration of the lysine-derived units was established by Marfey's analysis, whereas that of C-9, 9′, and 9″ was determined via the circular dichroism data of the [Rh2(OCOCF3)4] complex and DFT NMR calculations. Thalassosamide showed moderate in vivo efficacy against Pseudomonas aeruginosa.
Kinetic and Thermodynamic Considerations of the Bracketing Method: Entropy-Driven Proton-Transfer Reactions in a Fourier Transform Mass Spectrometer
Gorman, Gregory S.,Amster, I. Jonathan
, p. 1602 - 1607 (1993)
Several reports of experimentally derived proton affinity values and gas-phase basicity values for amino acids and peptides have recently appeared in the literature.Here, we show that the thermodynamic quantity that is measured by the Fourier transform mass spectrometry proton transfer bracketing of amino acids and peptides is gas-phase basicity and not proton affinity.Both experimental and theoretical evidence supports this conclusion.The difference between the values determined by proton transfer bracketing measurements for lysine versus leucine is consistent with a difference in gas-phase basicity rather than proton affinity.The rate of proton transfer from protonated lysine to a series of reference compounds have been measured.Entropy-driven, endothermic proton transfer is found to occur at the collision rate.Recent ab initio and semi-empirical calculations of the proton affinity of lysine are found to agree with the value that is derived from bracketing studies when one assumes that gas-phase basicity is measured.While entropy-driven reactions have been observed previously in high-pressure mass spectrometers, this is the first evidence for such reactions at low pressure in a Fourier transform mass spectrometer.
Photocatalytic Racemization of Amino Acids in Aqueous Polycrystalline Cadmium(II) Sulfide Dispersions
Ohtani, Bunsho,Kawaguchi, Jun-ichi,Kozawa, Masami,Nishimoto, Sei-ichi,Inui, Tomoyuki,Izawa, Kunisuke
, p. 1103 - 1110 (1995)
L-Lysine in an aqueous solution is partly racemized by photoirradiation (at wavelengths > 300 nm) in the presence of suspended cadmium(II) sulfide particles under a de-aerated atmosphere at room temperature.Loading of a small amount of platinum or its oxide inhibited the racemization, but enhanced N-cyclization of L-lysine into DL-pipecolinic acid. 2H and 1H NMR measurements of the racemate from photoirradiated reaction mixtures in deuterium oxide solutions revealed the substitution of the α-hydrogen of lysine with deuterium alongside the racemization.These facts suggest a mechanism for photocatalytic racemization that includes both reduction and oxidation by photoexcited electrons and positive holes, respectively.Similarly, the other amino acids, leucine and phenylalanine, undergo photocatalytic racemization under reaction conditions where the α-amino group is deprotonated, although glutamic acid gives no racemate during photocatalytic decomposition.Among the CdS photocatalysts used in this study, well grown cubic crystallites with a specific surface area of ca. 8 m2 g-1 showed the highest selectivity for the racemization of L-lysine.
Solution kinetics of a water-soluble hydrocortisone prodrug: Hydrocortisone-21-lysinate
Johnson,Amidon,Pogany
, p. 87 - 89 (1985)
Hydrocortisone-21-lysinate was synthesized as an amino acid prodrug of hydrocortisone to serve as a substrate for brush border aminopeptidases. This strategy was developed to demonstrate that an improvement in oral absorption could be obtained through reconversion in vivo. The aqueous stability of hydrocortisone-21-lysinate was studied over the pH range 3-8 at 25 °C. Reversible acyl migration of the lysine group between the 21- and 17-position hydroxyl groups was observed as well as hydrolysis. The observed half-life for direct hydrolysis of hydrocortisone-21-lysinate is 40 d at pH 3 and 30 min at pH 7. The relative instability at pH 7 is probably due to electrostatic stabilization of the negatively charged tetrahedral intermediate by the protonated amino groups.
Trimethylsilyl Trifluoromethanesulphonate as a Useful Deprotecting Reagent in Both Solution and Solid Phase Peptide Syntheses
Fujii, Nobutaka,Otaka, Akira,Ikemura, Osamu,Akaji, Kenichi,Funakoshi, Susumu,et al.
, p. 274 - 275 (1987)
Trimethylsilyl trifluoromethanesulphonate in trifluoroacetic acid has been found to cleave, in the presence of thioaisole, a number of protecting groups currently employed in peptide synthesis, without significant side reactions and with a much faster rate of reaction than trifluoromethanesulphonic acid in trifluoroacetic acid; this new deprotecting reagent has been used in solution and solid phase peptide syntheses of neuromedin U-25 (a 25-residue peptide) and a rabbit stomach peptide (an 8-residue peptide), respectively.
Binding Methylarginines and Methyllysines as Free Amino Acids: A Comparative Study of Multiple Host Classes**
Warmerdam, Zoey,Kamba, Bianca E.,Le, My-Hue,Schrader, Thomas,Isaacs, Lyle,Bayer, Peter,Hof, Fraser
, (2021/11/30)
Methylated free amino acids are an important class of targets for host-guest chemistry that have recognition properties distinct from those of methylated peptides and proteins. We present comparative binding studies for three different host classes that are each studied with multiple methylated arginines and lysines to determine fundamental structure-function relationships. The hosts studied are all anionic and include three calixarenes, two acyclic cucurbiturils, and two other cleft-like hosts, a clip and a tweezer. We determined the binding association constants for a panel of methylated amino acids using indicator displacement assays. The acyclic cucurbiturils display stronger binding to the methylated amino acids, and some unique patterns of selectivity. The two other cleft-like hosts follow two different trends, shallow host (clip) following similar trends to the calixarenes, and the other more closed host (tweezer) binding certain less-methylated amino acids stronger than their methylated counterparts. Molecular modelling sheds some light on the different preferences of the various hosts. The results identify hosts with new selectivities and with affinities in a range that could be useful for biomedical applications. The overall selectivity patterns are explained by a common framework that considers the geometry, depth of binding pockets, and functional group participation across all host classes.
DISCOVERY, TOTAL SYNTHESIS, AND BIOACTIVITY OF DOSCADENAMIDES
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Page/Page column 81; 84-85, (2021/02/05)
The invention is directed towards compounds (e.g., Formulae (I)-(IX)), their mechanism of action, processes to prepare the compounds, methods of activating quorum sensing signaling activity, and methods of treating diseases and disorders using the compounds described herein (e.g., Formulae (I)-(IX)).
