Hollenhorst, Marie A’s team published research in Biochemistry in 2009-11-03 | 77215-54-4

Biochemistry published new progress about Antibiotics (dapdiamides). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Formula: C12H24N2O4.

Hollenhorst, Marie A.; Clardy, Jon; Walsh, Christopher T. published the artcile< The ATP-Dependent Amide Ligases DdaG and DdaF Assemble the Fumaramoyl-Dipeptide Scaffold of the Dapdiamide Antibiotics>, Formula: C12H24N2O4, the main research area is DdaG DdaF ATP dependent amide ligase assembly dapdiamide antibiotic.

The enzymes DdaG and DdaF, encoded in the Pantoea agglomerans dapdiamide antibiotic biosynthetic gene cluster, when expressed in Escherichia coli, form the tandem amide bonds of the dapdiamide scaffold at the expense of ATP cleavage. DdaG uses fumarate, 2,3-diaminopropionate (DAP), and ATP to make fumaroyl-AMP transiently on the way to the Nβ-fumaroyl-DAP regioisomer. Then DdaF acts as a second ATP-dependent amide ligase, but this enzyme cleaves ATP to ADP and Pi during amide bond formation. However, DdaF will not accept Nβ-fumaroyl-DAP; the enzyme requires the fumaroyl moiety to be first converted to the fumaramoyl half-amide in Nβ-fumaramoyl-DAP. DdaF adds Val, Ile, or Leu to the carboxylate of fumaramoyl-DAP to make dapdiamide A, B, or C, resp. Thus, to build the dapdiamide antibiotic scaffold, amidation must occur on the fumaroyl-DAP scaffold, after DdaG action but before DdaF catalysis. This is an unusual instance of two ligases acting sequentially in untemplated amide bond formations using attack of substrate carboxylates at Pα (AMP-forming) and then at Pγ (ADP-forming) of ATP co-substrates.

Biochemistry published new progress about Antibiotics (dapdiamides). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Formula: C12H24N2O4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

More, Swati S’s team published research in Bioorganic & Medicinal Chemistry Letters in 2006-12-01 | 77215-54-4

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Quality Control of 77215-54-4.

More, Swati S.; Vince, Robert published the artcile< A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I>, Quality Control of 77215-54-4, the main research area is glutathione analog urea isostere preparation inhibition glyoxalase I antitumor.

The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the Glu-Cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistance toward γ-glutamyltranspeptidase mediated breakdown. This compound is viewed as a potential lead for the development of second-generation glyoxalase-I inhibitors wherein, the problems pertaining to metabolism and selectivity are overcome.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Quality Control of 77215-54-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

More, Swati S’s team published research in Journal of Medicinal Chemistry in 2009-08-13 | 77215-54-4

Journal of Medicinal Chemistry published new progress about Enzyme functional sites, active. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Reference of 77215-54-4.

More, Swati S.; Vince, Robert published the artcile< Inhibition of Glyoxalase I: The First Low-Nanomolar Tight-Binding Inhibitors>, Reference of 77215-54-4, the main research area is glutathione based peptide hydroxamate preparation low nanomolar inhibitor glyoxalase.

A series of rational modifications to the structure of known S-(N-aryl-N-hydroxycarbamoyl)glutathione-based glyoxalase I inhibitors culminated in the discovery of the first single-digit nanomolar inhibitor. This study makes available key information about possible means to address the issues of metabolic instability, low potency, and synthetic complexity that have plagued the area of glyoxalase I inhibition. Knowledge garnered from this study has implications in the design of inhibitors with higher conformational definition and lower peptidic character.

Journal of Medicinal Chemistry published new progress about Enzyme functional sites, active. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Reference of 77215-54-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Kubota, Dai’s team published research in Bioorganic & Medicinal Chemistry in 2006-06-15 | 77215-54-4

Bioorganic & Medicinal Chemistry published new progress about Integrin αIIbβ3 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, HPLC of Formula: 77215-54-4.

Kubota, Dai; Ishikawa, Minoru; Ishikawa, Midori; Yahata, Naokazu; Murakami, Shoichi; Fujishima, Kazuyuki; Kitakaze, Masafumi; Ajito, Keiichi published the artcile< Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part IV: Preliminary control of αvβ3 selectivity by meta-oriented substitution>, HPLC of Formula: 77215-54-4, the main research area is piperazine piperidine based integrin antagonist preparation SAR.

To establish the in vivo efficacy of αvβ3/αIIbβ3 dual antagonists possessing a tricyclic pharmacophore, a corresponding αvβ3-selective antagonist was required as a control. We initially took two synthetic approaches to obtain αvβ3-selective antagonists based on the RGD recognition pattern or on modification of the dihedral angle between the central benzene ring and the adjacent heterocycle, but both proved unsuccessful. However, synthesis of novel antagonists with meta-substitution of the central benzene ring generated weak selectivity for αvβ3 over αIIbβ3 for the first time in the family of compounds with the tricyclic pharmacophore. Optimization of meta-oriented antagonists furnished an αvβ3-selective antagonist exhibiting inhibitory activity not only in a receptor-binding assay, but also in a cell adhesion assay.

Bioorganic & Medicinal Chemistry published new progress about Integrin αIIbβ3 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, HPLC of Formula: 77215-54-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hollenhorst, Marie A’s team published research in Journal of the American Chemical Society in 2011-02-09 | 77215-54-4

Journal of the American Chemical Society published new progress about Antibiotics (dapdiamide). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Quality Control of 77215-54-4.

Hollenhorst, Marie A.; Bumpus, Stefanie B.; Matthews, Megan L.; Bollinger, J. Martin; Kelleher, Neil L.; Walsh, Christopher T. published the artcile< The Nonribosomal Peptide Synthetase Enzyme DdaD Tethers Nβ-Fumaramoyl-L-2,3-diaminopropionate for Fe(II)/α-Ketoglutarate-Dependent Epoxidation by DdaC during Dapdiamide Antibiotic Biosynthesis. [Erratum to document cited in CA153:612347]>, Quality Control of 77215-54-4, the main research area is erratum peptide synthetase DdaD epoxidation DdaC DdaF dapdiamide; Pantoea nonribosomal peptide synthetase DdaD epoxidation erratum.

On Supporting Information page S5, the addition of one equivalent of N-methlymorpholine was omitted from the methods for preparation of amides 2a and 2b. The reagent was added prior to cooling the solutions to -10 °C. On Supporting Information page S7, the wording of the method section ‘G. DdaC/D Enzymic Assays with Anaerobically Purified Ddac’ was altered to make it more clear. This material is available free of charge via the Internet at http://pubs.acs.organic

Journal of the American Chemical Society published new progress about Antibiotics (dapdiamide). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Quality Control of 77215-54-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hollenhorst, Marie A’s team published research in Journal of the American Chemical Society in 2010-11-10 | 77215-54-4

Journal of the American Chemical Society published new progress about Antibiotics (dapdiamide). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Recommanded Product: (S)-tert-Butyl 3-amino-2-((tert-butoxycarbonyl)amino)propanoate.

Hollenhorst, Marie A.; Bumpus, Stefanie B.; Matthews, Megan L.; Bollinger, J. Martin Jr.; Kelleher, Neil L.; Walsh, Christopher T. published the artcile< The Nonribosomal Peptide Synthetase Enzyme DdaD Tethers Nβ-Fumaramoyl-L-2,3-diaminopropionate for Fe(II)/α-Ketoglutarate-Dependent Epoxidation by DdaC during Dapdiamide Antibiotic Biosynthesis>, Recommanded Product: (S)-tert-Butyl 3-amino-2-((tert-butoxycarbonyl)amino)propanoate, the main research area is Pantoea nonribosomal peptide synthetase DdaD epoxidation DdaC DdaF dapdiamide.

The gene cluster from Pantoea agglomerans responsible for biosynthesis of the dapdiamide antibiotics encodes an adenylation-thiolation didomain protein, DdaD, and an Fe(II)/α-ketoglutarate-dependent dioxygenase homolog, DdaC. Here we show that DdaD, a nonribosomal peptide synthetase module, activates and sequesters Nβ-fumaramoyl-L-2,3-diaminopropionate as a covalently tethered thioester for subsequent oxidative modification of the fumaramoyl group. DdaC catalyzes Fe(II)- and α-ketoglutarate-dependent epoxidation of the covalently bound Nβ-fumaramoyl-L-2,3-diaminopropionyl-S-DdaD species to generate Nβ-epoxysuccinamoyl-DAP (DAP = 2,3-diaminopropionate) in thioester linkage to DdaD. After hydrolytic release, Nβ-epoxysuccinamoyl-DAP can be ligated to L-valine by the ATP-dependent ligase DdaF to form the natural antibiotic Nβ-epoxysuccinamoyl-DAP-Val.

Journal of the American Chemical Society published new progress about Antibiotics (dapdiamide). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Recommanded Product: (S)-tert-Butyl 3-amino-2-((tert-butoxycarbonyl)amino)propanoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

More, Swati S’s team published research in Journal of Medicinal Chemistry in 2008-08-14 | 77215-54-4

Journal of Medicinal Chemistry published new progress about Antiparkinsonian agents. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Application of C12H24N2O4.

More, Swati S.; Vince, Robert published the artcile< Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugs>, Application of C12H24N2O4, the main research area is glutathione peptidomimetic synthesis antiParkinson prodrug uptake blood brain barrier; peptide drug design antiParkinson prodrug CNS plasma disulfide bond; glucitol doramine oxidation regioselective epoxide opening peptide coupling adamantine.

Plethoras of CNS-active drugs fail to effect their pharmacol. response due to their in vivo inability to cross the blood-brain barrier (BBB). The classical prodrug approach to overcome this frailty involves lipophilic derivatives of the polar drug, but we herein report a novel approach by which endogenous transporters at BBB are exploited for brain drug delivery. The crucial role played by glutathione in pathogenesis of Parkinson’s and the presence of its influx transporters at the basolateral membrane of BBB served as the basis for our anti-Parkinson prodrug design strategy. A metabolically stable analog [I, R1 = adamantamine or (II)] of glutathione is used as a carrier for delivery of dopamine and adamantamine. An account of successful syntheses of these prodrugs along with their transport characteristics and stability determination is discussed.

Journal of Medicinal Chemistry published new progress about Antiparkinsonian agents. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Application of C12H24N2O4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Moali, Catherine’s team published research in Biochemistry in 2000-07-18 | 77215-54-4

Biochemistry published new progress about Enzyme functional sites, active. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Recommanded Product: (S)-tert-Butyl 3-amino-2-((tert-butoxycarbonyl)amino)propanoate.

Moali, Catherine; Brollo, Maurice; Custot, Julien; Sari, Marie-Agnes; Boucher, Jean-Luc; Stuehr, Dennis J.; Mansuy, Daniel published the artcile< Recognition of α-Amino Acids Bearing Various C:NOH Functions by Nitric Oxide Synthase and Arginase Involves Very Different Structural Determinants>, Recommanded Product: (S)-tert-Butyl 3-amino-2-((tert-butoxycarbonyl)amino)propanoate, the main research area is hydroxyguanidine amino acid preparation arginase recognition; amidoxime amino acid preparation nitric oxide synthase recognition; amino acid recognition arginase nitric oxide synthase.

Several α-amino acids bearing a C:NOH function separated from the Cα carbon by two to five atoms have been synthesized and tested as substrates or inhibitors of recombinant nitric oxide synthases (NOS) I and II and as inhibitors of rat liver arginase (RLA). These include four N-hydroxyguanidines, Nω-hydroxy-L-arginine (NOHA) and its analogs homo-NOHA, nor-NOHA, and dinor-NOHA, two amidoximes bearing the -NH-C(CH3):NOH group, and two amidoximes bearing the -CH2-C(NH2):NOH group. Their behavior toward NOS and RLA was compared to that of the corresponding compounds bearing a C:NH function instead of the C:NOH function. The results obtained clearly show that efficient recognition of these α-amino acids by NOS and RLA involves very different structural determinants. NOS favors mols. bearing a -NH-C(R):NH motif separated from Cα by three or four CH2 groups – such as arginine itself – with the necessary presence of δ-NH and ω-NH groups and a more variable R substituent. The corresponding mols. with a C:NOH function exhibit a much lower affinity for NOS. On the contrary, RLA best recognizes mols. bearing a C:NOH function separated from Cα by three or four atoms, the highest affinity being observed in the case of three atoms. The presence of two ω-nitrogen atoms is important for efficient recognition, as in the two best RLA inhibitors, Nω-hydroxynorarginine and Nω-hydroxynorindospicine, which exhibit IC50 values at the micromolar level. However, contrary to what was observed in the case of NOS, the presence of a δ-NH group is not important. These different structural requirements of NOS and RLA may be directly linked to the position of crucial residues that have been identified from crystallog. data in the active sites of both enzymes. Thus, binding of arginine analogs to NOS particularly relies on strong interactions of their δ-NH and ω-NH2 groups with glutamate 371 (of NOS II), whereas binding of C:NOH mols. to RLA is mainly based on interactions of their terminal OH group with the binuclear Mn(II)···Mn(II) cluster of the enzyme and on possible addnl. bonds between their ω-NH2 group with histidine 141, glutamate 277, and one Mn(II) ion. The different modes of interaction displayed by both enzymes depend on their different catalytic functions and provide interesting opportunities to design useful mols. for selective regulation of NOS and arginase.

Biochemistry published new progress about Enzyme functional sites, active. 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Recommanded Product: (S)-tert-Butyl 3-amino-2-((tert-butoxycarbonyl)amino)propanoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zou, Ying’s team published research in Journal of the American Chemical Society in 2002-08-14 | 77215-54-4

Journal of the American Chemical Society published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Formula: C12H24N2O4.

Zou, Ying; Fahmi, Nour Eddine; Vialas, Corine; Miller, Guy M.; Hecht, Sidney M. published the artcile< Total Synthesis of Deamido Bleomycin A2, the Major Catabolite of the Antitumor Agent Bleomycin>, Formula: C12H24N2O4, the main research area is deamido bleomycin A2 total synthesis; demethyl deamido bleomycin A2 total synthesis; aglycon deamido bleomycin A2 total synthesis; DNA relaxation cleavage deamido bleomycin A2.

This work describes the synthesis of deamido-demethyl-bleomycin A2, I (R = SMe) and deamido-bleomycin A2, I (R = SMe2), as well as their resp. aglycons. Amino ester II was the key intermediate for I. Synthetic deamido-bleomycin A2 was shown to be identical to the product formed by treatment of bleomycin A2 (BLM-A2) with bleomycin hydrolase, as judged by reversed-phase HPLC anal. and 1H NMR spectroscopy. Deamido-bleomycin A2 was found to retain significant DNA cleavage activity in DNA plasmid relaxation assays and had the same sequence selectivity of DNA cleavage as bleomycin A2. The most significant alteration of function noted in this study was a reduction in the ability of deamido-bleomycin A2 to mediate double-strand DNA cleavage, relative to that produced by BLM-A2.

Journal of the American Chemical Society published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Formula: C12H24N2O4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zou, Ying’s team published research in Journal of the American Chemical Society in 2002-08-14 | 77215-54-4

Journal of the American Chemical Society published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Formula: C12H24N2O4.

Zou, Ying; Fahmi, Nour Eddine; Vialas, Corine; Miller, Guy M.; Hecht, Sidney M. published the artcile< Total Synthesis of Deamido Bleomycin A2, the Major Catabolite of the Antitumor Agent Bleomycin>, Formula: C12H24N2O4, the main research area is deamido bleomycin A2 total synthesis; demethyl deamido bleomycin A2 total synthesis; aglycon deamido bleomycin A2 total synthesis; DNA relaxation cleavage deamido bleomycin A2.

This work describes the synthesis of deamido-demethyl-bleomycin A2, I (R = SMe) and deamido-bleomycin A2, I (R = SMe2), as well as their resp. aglycons. Amino ester II was the key intermediate for I. Synthetic deamido-bleomycin A2 was shown to be identical to the product formed by treatment of bleomycin A2 (BLM-A2) with bleomycin hydrolase, as judged by reversed-phase HPLC anal. and 1H NMR spectroscopy. Deamido-bleomycin A2 was found to retain significant DNA cleavage activity in DNA plasmid relaxation assays and had the same sequence selectivity of DNA cleavage as bleomycin A2. The most significant alteration of function noted in this study was a reduction in the ability of deamido-bleomycin A2 to mediate double-strand DNA cleavage, relative to that produced by BLM-A2.

Journal of the American Chemical Society published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 77215-54-4 belongs to class esters-buliding-blocks, and the molecular formula is C12H24N2O4, Formula: C12H24N2O4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics