498-40-8Relevant academic research and scientific papers
N-Phenylacetylation and Nonribosomal Peptide Synthetases with Substrate Promiscuity for Biosynthesis of Heptapeptide Variants, JBIR-78 and JBIR-95
Takeda, Kunpei,Kemmoku, Kohei,Satoh, Yasuharu,Ogasawara, Yasushi,Shin-Ya, Kazuo,Dairi, Tohru
, p. 1813 - 1819 (2017/07/26)
JBIR-78 (1) and JBIR-95 (2), both of which are heptapeptide derivatives isolated from Kibdelosporangium sp. AK-AA56, have the same amino acid sequences except for the second amino acid: phenylacetic acid (Paa)-l-Val-d-Asp (1)/d-cysteic acid (2)-l-Ala-(3S)-3-hydroxy-d-Leu-Gly-d-Ala-l-Phe. Heterologous expression of the biosynthetic gene cluster including genes encoding nonribosomal peptide synthetases (NRPS) and in vitro assays with recombinant Orf3, an l-cysteic acid synthase homologue, suggested the single A domain in module 2 activates both l-Asp and l-cysteic acid to yield 1 and 2, respectively, although the substrate specificities of the A domains of NRPSs are usually strict. Biosynthetic mechanism of introduction of N-terminal Paa was also investigated. Recombinant Orf1 and Orf2 similar to subunits of pyruvate dehydrogenase complex catalyzed the conversion of phenylpyruvate into phenylacetyl-CoA together with dihydrolipoyl dehydrogenase whose encoding gene is located outside of the gene cluster. Moreover, we showed that phenylacetyl-CoA was directly condensed with l-Val, which was tethered to a peptidyl carrier protein, at the first condensation domain in the NRPS.
Synthesis of sulfonyl chlorides and sulfonic acids in SDS micelles
Bahrami, Kiumars,Khodaei, Mohammad M.,Abbasi, Jamshid
experimental part, p. 316 - 322 (2012/03/26)
H2O2/POCl3 is found to be a reactive reagent system that can be used in sodium dodecyl sulfate (SDS) micellar solution in aqueous media for the direct oxidative chlorination of thiol and di-sulfide derivatives to give the desired sulfonyl chlorides. The oxidation of thiols and disulfides to sulfonic acids with this system is also reported. In most cases, these reactions are highly selective, simple, and clean, affording products in excellent yields and high purity. Georg Thieme Verlag Stuttgart · New York.
Formation of the bisulfite anion (HSO3 -, m/z 81) upon collision-induced dissociation of anions derived from organic sulfonic acids
Jariwala, Freneil B.,Wood, Ryan E.,Nishshanka, Upul,Attygalle, Athula B.
experimental part, p. 529 - 538 (2012/08/28)
In the negative-ion collision-induced dissociation mass spectra of most organic sulfonates, the base peak is observed at m/z 80 for the sulfur trioxide radical anion (SO3 -·). In contrast, the product-ion spectra of a few sulfonates, such as cysteic acid, aminomethanesulfonate, and 2-phenylethanesulfonate, show the base peak at m/z 81 for the bisulfite anion (HSO3 - ). An investigation with an extensive variety of sulfonates revealed that the presence of a hydrogen atom at the β-position relative to the sulfur atom is a prerequisite for the formation of the bisulfite anion. The formation of HSO3 - is highly favored when the atom at the β-position is nitrogen, or the leaving neutral species is a highly conjugated molecule such as styrene or acrylic acid. Deuterium-exchange experiments with aminomethanesulfonate demonstrated that the hydrogen for HSO3 - formation is transferred from the β-position. The presence of a peak at m/z 80 in the spectrum of 2-sulfoacetic acid, in contrast to a peak at m/z 81 in that of 3-sulfopropanoic acid, corroborated the proposed hydrogen transfer mechanism. For diacidic compounds, such as 4-sulfobutanoic acid and cysteic acid, the m/z 81 ion can be formed by an alternative mechanism, in which the negative charge of the carboxylate moiety attacks the α-carbon relative to the sulfur atom. Experiments conducted with deuterium-exchanged and deuterium-labeled analogs of sulfocarboxylic acids demonstrated that the formation of the bisulfite anion resulted either from a hydrogen transfer from the β-carbon, or from a direct attack by the carboxylate moiety on the α-carbon. Copyright
Thailandepsins: Bacterial products with potent histone deacetylase inhibitory activities and broad-spectrum antiproliferative activities
Wang, Cheng,Henkes, Leonhard M.,Doughty, Leah B.,He, Min,Wang, Difei,Meyer-Almes, Franz-Josef,Cheng, Yi-Qiang
supporting information; experimental part, p. 2031 - 2038 (2011/12/15)
Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum no. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9 but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI50 for over 90% of the tested cell lines at low nanomolar concentrations and potent cytotoxic activities toward certain types of cell lines, particularly for those derived from colon, melanoma, ovarian, and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development.
Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides
Kwan, Jason C.,Ratnayake, Ranjala,Abboud, Khalil A.,Paul, Valerie J.,Luesch, Hendrik
experimental part, p. 8012 - 8023 (2011/03/20)
Grassypeptolides A-C (1-3), a group of closely related bis-thiazoline containing cyclic depsipeptides, have been isolated from extracts of the marine cyanobacterium Lyngbya confervoides. Although structural differences between the analogues are minimal, comparison of the in vitro cytotoxicity of the series revealed a structure-activity relationship. When the ethyl substituent of 1 is changed to a methyl substituent in 2, activity is only slightly reduced (3-4-fold), whereas inversion of the Phe unit flanking the bis-thiazoline moiety results in 16-23-fold greater potency. We show that both 1 and 3 cause G1 phase cell cycle arrest at lower concentrations, followed at higher concentrations by G2/M phase arrest, and that these compounds bind Cu2+ and Zn 2+. The three-dimensional structure of 2 was determined by MS, NMR, and X-ray crystallography, and the structure of 3 was established by MS, NMR, and chemical degradation. The structure of 3 was explored by in silico molecular modeling, revealing subtle differences in overall conformation between 1 and 3. Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense.
Alotamide A, a novel neuropharmacological agent from the marine cyanobacterium Lyngbya bouillonii
Soria-Mercado, Irma E.,Pereira, Alban,Cao, Zhengyu,Murray, Thomas F.,Gerwick, William H.
supporting information; experimental part, p. 4704 - 4707 (2009/12/26)
Alotamide A (1), a structurally Intriguing cyclic depsipeptide, was isolated from the marine mat-forming cyanobacterlum Lyngbya bouillonii collected In Papua New Guinea. It features three contiguous peptidic residues and an unsaturated heptaketide with oxidations and methylations unlike those found In any other marine cyanobacterial metabolite. Pure alotamide A (1) displays an unusual calcium influx activation profile In murine cerebrocortical neurons with an EC50 of 4.18 uU.
Kinetics of oxidation of L-cystine by pyridinium bromochromate
Annapurna,Kumar, A. Kalyan,Vani,Rao, G. Nageswara
body text, p. 542 - 545 (2009/07/18)
The kinetics of oxidation of cystine by pyridinium bromochromate (PBC) was studied spcctrophotometrically under pseudo-first order conditions in perchloric acid medium at 370 nm. It was found that the reaction is first order in [PBC], fractional order in [cystine] and the reaction rate is increased with [H +] showing an order of more than unity. Product analysis confirmed cysteic acid as the final product of oxidation.
Functional group requirements within the peptide H-Pro-Pro-Asp-NH2 as a catalyst for aldol reactions
Revell, Jefferson D.,Wennemers, Helma
, p. 8420 - 8424 (2008/02/08)
H-Pro-Pro-Asp-NH2 1 is a versatile catalyst for asymmetric aldol reactions. In this work, the functional group tolerance within the catalyst structure has been examined. Several analogs of H-Pro-Pro-Asp-NH2 in which the N-terminal secondary amine or the carboxylic acid in the side chain of the aspartic acid residue is replaced by different functional groups were prepared. Evaluation of their catalytic properties revealed that both the N-terminal secondary amine and the carboxylic acid are important for catalysis. The implications for the reaction mechanism are discussed.
Antioxidant chemistry: Oxidation of L-cysteine and its metabolites by chlorite and chlorine dioxide
Darkwa, James,Olojo, Rotimi,Chikwana, Edward,Simoyi, Reuben H.
, p. 5576 - 5587 (2007/10/03)
The oxidation of L-cysteine and its metabolites cystine and L-cysteinesulfinic acid by chlorite and chlorine dioxide has been studied in unbuffered neutral and slightly acidic media. The stoichiometry of the oxidation of L-cysteine was deduced to be 3ClO2- + 2H 2NCH(COOH)CH2SH → 3Cl- + 2H 2NCH(COOH)CH2SO3H with the final product as cysteic acid. The stoichiometry of the chlorite-cysteinesulfinic acid gave a ratio of 1:2, ClO2- + 2H2NCH(COOH)CH 2SO2H → Cl- + 2H2NCH(COOH) CH2SO3H. There was no further oxidation past cysteic acid, and there was no evidence of sulfate formation which would have indicated the cleavage of the carbon-sulfur bond. The reaction is oligooscillatory in chlorine dioxide formation. In conditions of excess oxidant, the reaction is characterized by a short induction period followed by a rapid and autocatalytic formation of chlorine dioxide. Chlorine dioxide is formed by the reaction of intermediate HOCl with the excess chlorite: 2ClO2- + 2HOCl + H- → 2ClO2(aq) + Cl- + H2O. Oligooscillations observed in chlorine dioxide formation result from the competition between this pure oxyhalogen reaction and reactions that consume chlorine dioxide. The rate of the reaction of chlorine dioxide with cysteine and its metabolites is fast and is of comparable magnitude with the reactions that form chlorine dioxide. The reaction of chlorine dioxide with L-cysteine is first order in both oxidant and substrate, retarded by acid, and has a lower-limit bimolecular rate constant of 405 ± 50 M-1 s-1, while for the reaction with L-cysteinesulfinic acid the rate constant is 210 ± 15 M-1 s-1. It would appear that the existence of a zwitterion on the asymmetric carbon atom precludes the formation of N-chloramines as has been observed with taurine and aminomethanesulfonic acid. The mechanism for the reaction is satisfactorily described by a network of 28 elementary reactions which include autocatalysis by HOCl.
Synthesis of L-cysteine and L-cysteic acid by paired electrolysis method
Wang, Xixin,Zhao, Jianling
, p. 332 - 333 (2007/10/03)
L-Cysteine and L-cysteic acid were synthesized by paired eletrolysis method. A high purity over 98% and high yield over 90% of both products were gained. When current density was 7 A/dm2 and concentration of L-cysteine was 0.6 mol/dm3, the highest current efficiency of anode and cathode was achieved. Total current efficiency was over 180%. The cyclic voltammetry behaviors of hydrobromic acid and cystine showed that a typical EC reaction took place in the anodic cell. The anode reaction and successive chemical reaction accelerated each other to get a high speed and current efficiency.
