- Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres
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Hepsin is a type II transmembrane serine protease (TTSP) associated with cell proliferation and overexpressed in several types of cancer including prostate cancer (PCa). Because of its significant role in cancer progression and metastasis, hepsin is an attractive protein as a potential therapeutic and diagnostic biomarker for PCa. Based on the reported Leu-Arg dipeptide-based hepsin inhibitors, we performed structural modification and determined in vitro hepsin- and matriptase-inhibitory activities. Comprehensive structure-activity relationship studies identified that the p-guanidinophenylalanine-based dipeptide analog 22a exhibited a strong hepsin-inhibitory activity (Ki = 50.5 nM) and 22-fold hepsin selectivity over matriptase. Compound 22a could be a prototype molecule for structural optimization of dipeptide-based hepsin inhibitors.
- Kwon, Hongmok,Ha, Hyunsoo,Jeon, Hayoung,Jang, Jaebong,Son, Sang-Hyun,Lee, Kiho,Park, Song-Kyu,Byun, Youngjoo
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supporting information
(2020/12/25)
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- Bio- And Medicinally Compatible α-Amino-Acid Modification via Merging Photoredox and N-Heterocyclic Carbene Catalysis
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An N-heterocyclic carbene and photoredox cocatalyzed α-amino-acid decarboxylative carbonylation reaction is presented. This method displays good scope generality, providing a direct pathway to access various downstream α-amino ketones under bio- and medicinally compatible conditions. Moreover, this strategy is appealing to chemical biology because it has great potential for the chemical modification of peptides or the late-stage synthesis of keto-peptides.
- Chen, Lei,Du, Ding,Feng, Jie,Gao, Jian,Lu, Tao,Ma, Rui,Shi, Zhihao,Zhang, Kuili
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supporting information
(2020/09/02)
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- Oxidative Damage in Aliphatic Amino Acids and Di- and Tripeptides by the Environmental Free Radical Oxidant NO3?: the Role of the Amide Bond Revealed by Kinetic and Computational Studies
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Kinetic and computational data reveal a complex behavior of the important environmental free radical oxidant NO3? in its reactions with aliphatic amino acids and di- and tripeptides, suggesting that attack at the amide N-H bond in the peptide backbone is a highly viable pathway, which proceeds through a proton-coupled electron transfer (PCET) mechanism with a rate coefficient of about 1 × 106 M-1 s-1 in acetonitrile. Similar rate coefficients were determined for hydrogen abstraction from the α-carbon and from tertiary C-H bonds in the side chain. The obtained rate coefficients for the reaction of NO3? with aliphatic di- and tripeptides suggest that attack occurs at all of these sites in each individual amino acid residue, which makes aliphatic peptide sequences highly vulnerable to NO3?-induced oxidative damage. No evidence for amide neighboring group effects, which have previously been found to facilitate radical-induced side-chain damage in phenylalanine, was found for the reaction of NO3? with side chains in aliphatic peptides.
- Nathanael, Joses G.,Wille, Uta
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p. 3405 - 3418
(2019/03/11)
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- GRANZYME B DIRECTED IMAGING AND THERAPY
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Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
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Page/Page column 108; 109; 146
(2019/09/04)
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- Rapid Room-Temperature Gelation of Crude Oils by a Wetted Powder Gelator
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Phase-selective organogelators (PSOGs) not only exhibit ability to phase-selectively congeal oil from oily water but also allow easy separation of gelled oil from the body of water. However, all hitherto reported PSOGs either necessitate carrier solvents for their dissolution or suffer from an extremely slow action in gelling oil in the powder form. A previously unexplored generally applicable wetting strategy is now described to dramatically enhance, by up to two orders of magnitude, gelling speed of the resultant wet but non-sticky gelator in the powder form in crude oils of widely ranging viscosities. Such unprecedented rapid gelling speeds enable rapid gelation of six types of (un)weathered crude oils within minutes at room temperature, making PSOGs one step closer to their eventual practical uses as one of important oil spill control technologies.
- Ren, Changliang,Shen, Jie,Chen, Feng,Zeng, Huaqiang
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supporting information
p. 3847 - 3851
(2017/03/27)
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- AN ORGANOGELATOR COMPOUND
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An organogelator compound is provided. The organogelator compound has Formula (I): wherein R1, R2, and R3 are independently selected from the group consisting of H, halogen, a substituted or unsubstituted C1-C20 alkyl, a substituted or unsubstituted C1-C20 alkoxy, a substituted or unsubstituted C2-C20 alkenyl, a substituted or unsubstituted C2-C20 alkynyl, a substituted or unsubstituted C3-C20 alicyclic group, a substituted or unsubstituted C5-C15 aryl, a substituted or unsubstituted C6-C30 alkyl-aryl, a substituted or unsubstituted C3-C20 heterocycle, a substituted or unsubstituted C4-C30 alkyl-heterocycle, a substituted or unsubstituted C5-C15 heteroaryl, -NRR', -NR, -OR, -SR, -CN, -NO2, -C(O)-R, -COOR, -NR'- C(O)-R, -C(O)-NRR', -C(NR)-R', -SO2-R, -(SO2)-OR, -C(S)-R, and -C(S)-NRR'; and R and R' are independently selected from the group consisting of H, halogen, a substituted or unsubstituted C1-C20 alkyl, a substituted or unsubstituted C1-C20 alkoxy, a substituted or unsubstituted C2-C20 alkenyl, a substituted or unsubstituted C2-C20 alkynyl, and a substituted or unsubstituted C5-C15 aryl. A method of gelating an oil and an organic solvent having a Polarity Index of less than 3 is also provided.
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Paragraph 00168; 00169
(2017/03/23)
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- Jamaicensamide A, a Peptide Containing β-Amino-α-keto and Thiazole-Homologated η-Amino Acid Residues from the Sponge Plakina jamaicensis
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A new cyclic peptide, jamaicensamide A, composed of six amino acids, including a thiazole-homologated amino acid, was isolated from the Bahamian sponge Plakina jamaicensis, along with known compounds bitungolide A and franklinolide A. The structure of the title peptide was solved by integrated analysis of MS, 1D and 2D NMR data, oxidation-hydrolyses to α-amino acids, and their stereodetermination by Marfey's method. The close structural resemblance of Western Atlantic-derived jamaicensamide A to known Western Pacific-derived peptides of lithistid sponges in the genus Theonella and Discodermia suggests a common origin: the symbiotic bacterium Entotheonella sp., a so-called "talented producer" responsible for biosynthesis of most Theonella-associated peptides. Similar natural products from sponges of disparate genera evince the likelihood that these invertebrates harbor the same or a very similar symbiont.
- Jamison, Matthew T.,Molinski, Tadeusz F.
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supporting information
p. 2243 - 2249
(2016/10/04)
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- Peptide Tyrosinase Activators
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Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
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- Aqueous MW eco-friendly protocol for amino group protection
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In this paper a new catalyst-free and on-water method for protection of amines and amino acids with di-tert-butyl dicarbonate, 9-fluorenylmethoxycarbonyl chloride, acetyl chloride and tosyl chloride is presented. The protection can be realized in a few minutes under microwave-assistance. The reaction proved to be chemoselective in presence of ambident nucleophiles and water solution of di-tert-butyl carboxylic acid or chloride acid are the only wastes produced.
- Nardi,Cano, N. Herrera,Costanzo,Oliverio,Sindona,Procopio
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p. 18751 - 18760
(2015/06/15)
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- Synergistic interplay of a non-heme iron catalyst and amino acid coligands in H2O2 activation for asymmetric epoxidation of α-alkyl-substituted styrenes
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Highly enantioselective epoxidation of α-substituted styrenes with aqueous H2O2 is described by using a chiral iron complex as the catalyst and N-protected amino acids (AAs) as coligands. The amino acids synergistically cooperate with the iron center in promoting an efficient activation of H2O2 to catalyze epoxidation of this challenging class of substrates with good yields and stereoselectivities (up to 97% ee) in short reaction times.
- Cuss, Olaf,Ribas, Xavi,Lloret-Fillol, Julio,Costas, Miquel
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supporting information
p. 2729 - 2733
(2015/03/04)
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- Flavour Modifying Compounds
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A compound of formula (I) is used to modify the taste or flavour of a flavour composition or consumable product, wherein R1 is H, or a substituted, unsubstituted, branched or unbranched C1-C5 alkyl group and, NHR2 is a residue of an amino acid, is selected from Alanine (Ala), cysteine (Cys), Aspartic acid (Asp), phenylalanine (Phe), glutamic acid (Glu), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), methionine (Met), asparagines (Asn), glutamine (Gln), arginine (Arg), serine (Ser), theronine (Thr), valine (Val), tryptophan (Trp), tyrosine(Tyr) and Glycine (Gly), with the proviso that the compound is not N-acetyl glycine. Also disclosed are flavour compositions and consumable products containing such compounds.
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Page/Page column
(2014/05/20)
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- Preparation of N-acetyl, tert-butyl amide derivatives of the 20 natural amino acids
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N-Acetyl-AA(amino acid)-NHtBu derivatives of all 20 naturally occurring amino acids have been synthesized. Syntheses were performed via solution-phase methodology with yields that allow for access to gram quantities of substrates, in most cases. Syntheses include the coupling of a hindered amine, tert-butylamine, with each amino acid, either directly or in two steps using an activated ester isolated as an intermediate. The introduction of protecting groups was necessary in some cases. The development of synthetic sequences to access challenging substrates, such as the one derived from asparagine, are discussed.
- Ekkati,Campanali,Abouelatta,Shamoun,Kalapugama,Kelley,Kodanko, Jeremy J.
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body text
p. 747 - 751
(2010/08/05)
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- Structures and properties of a diastereoisomeric molecular compound of (2S,3S)- and (2R,3S)-N-acetyl-2-amino-3-methylpentanoic acids
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An X-ray crystal structural analysis revealed that (2S,3S)-N-acetyl-2- amino-3-methylpentanoic acid (N- acetyl-l-isoleucine; Ac-l-I1e) and (2R,3S)-N-acetyl-2- amino-3-methylpentanoic acid (N-acetyl-d-alloisoleucine; Ac-d-aIle) formed a molecular compound containing one Ac-l-Ile molecule and one Ac-d-aIle molecule as an unsymmetrical unit. This molecular compound is packed with strong hydrogen bonds forming homogeneous chains consisting of Ac-l-Ile molecules or Ac-d- aIle molecules and weak hydrogen bonds connecting these homogeneous chains in a fashion similar to that observed for Ac-l-Ile and Ac-d-aIle. Recrystallization of an approximately 1:1 mixture of Ac-l-Ile and Ac-d-aIle from water gave an equimolar molecular compound due to its lower solubility than that of Ac-d-aIle or especially Ac-l-Ile. The results suggest that the equimolar mixture of Ac-l-Ile and Ac-d-aIle could be obtained from an Ac-l-Ile-excess mixture by recystallization from water.
- Yajima, Tatsuo,Kimura, Makiko,Nakakoji, Mami,Horikawa, Takao,Tokuyama, Yurie,Shiraiwa, Tadashi
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experimental part
p. 2293 - 2298
(2010/07/17)
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- Lipase activity of Lecitase Ultra: characterization and applications in enantioselective reactions
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The general properties of Lecitase Ultra, a phospholipase manufactured and marketed by Novozymes, Denmark, have been studied after purification by ultrafiltration. The enzyme has a molecular mass of 35 KD, pH-optimum of 8.5, and appears to possess a single active site which exhibits both the lipase and phospholipase activities that increase in the presence of Ca2+ and Mg2+ ions. The enzyme is inhibited by heavy metal ions and surfactants, and does not accept p-nitrophenyl acetate and glycerol triacetate. Substrates, such as glycerol tributyrate and p-nitrophenyl palmitate, esters of N-acetyl-α-amino acids and α-hydroxy acids are readily accepted. Amino acids with aliphatic residues, such as alanine, isoleucine, and methionine, are hydrolyzed with high enantioselectivity for the l-enantiomer (E >100), but amino acids with aromatic residues such as phenylalanine and phenylglycine, and esters of α-hydroxy acids are hydrolyzed with low enantioselectivity (E = 1-5). Immobilization of the enzyme in a gelatin matrix (gelozyme) leads to a marginal improvement in the enantioselectivity for these substrates. However, a dramatic improvement in enantioselectivity is observed for ethyl 2-hydroxy-4-oxo-4-phenylbutyrate (E value increases from 4.5 to 19.5 with S-selectivity). Similarly, glycidate esters, such as ethyl trans-(±)-3-phenyl glycidate and methyl trans-(±)-3-(4-methoxyphenyl) glycidate, are selectively hydrolyzed with a remarkable selectivity towards the (2S,3R)-enantiomer providing unreacted (2R,3S)-glycidate esters (ee >99%, conversion 52-55%) by the immobilized enzyme.
- Mishra, Mithilesh Kumar,Kumaraguru, Thenkrishnan,Sheelu, Gurrala,Fadnavis, Nitin W.
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experimental part
p. 2854 - 2860
(2010/04/05)
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- Stereoselective incorporation of isoleucine into cypridina luciferin in Cypridina hilgendorfii (Vargula hilgendorfii)
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The emission of light in the marine ostracod Cypridina hilgendorfii (presently Vargula hilgendorfii) is produced by the Cypridina luciferin-luciferase reaction in the presence of molecular oxygen. Cypridina luciferin has an asymmetric carbon derived from isoleucine, and the absolute configuration is identical to the C-3 position in L-isoleucine or D-alloisoleucine. To determine the stereoselective incorporation of the isoleucine isomers (L-isoleucine, D-isoleucine, L-alloisoleucine, and D-alloisoleucine), we synthesized four 2H-labeled isoleucine isomers and examined their incorporation into Cypridina luciferin by feeding experiments. Judging by these results, L-isoleucine is predominantly incorporated into Cypridina luciferin. This suggests that the isoleucine unit of Cypridina luciferin is derived from L-isoleucine, but not from D-alloisoleucine.
- Kato, Shin-Ichi,Oba, Yuichi,Ojika, Makoto,Inouye, Satoshi
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p. 1528 - 1532
(2008/02/13)
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- Chemo-enzymatic approach to D-allo-isoleucine
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A mixture of D-alloisoleucine and L-isoleucine derivatives are selectively hydrolysed by enzymatic catalysis (alcalase) allowing the recovery of the D-allo stereoisomer in excellent d.e. and yields. Thus, N-formyl-D-allo- isoleucine benzylester is obtained after enzymatic hydrolysis of the diastereoisomeric mixture or by a crystallisation procedure.
- Cambie, Mara,D'Arrigo, Paola,Fasoli, Ezio,Servi, Stefano,Tessaro, Davide,Canevotti, Francesco,Del Corona, Lucio
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p. 3189 - 3196
(2007/10/03)
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- Pronase catalysed peptide syntheses
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A mixture of proteases from Streptomyces griseus (pronase), displaying a very broad substrate tolerance in the hydrolysis of peptides, has been studied for the first time systematically regarding their substrate specificity in peptide synthesis. It is demonstrated that pronase can be employed successfully for the formation of dipeptides with yields up to 95%. Pronase has also been employed successfully as catalyst for the enzyme assisted synthesis of a hexapeptide.
- Lobell, Mario,Schneider, Manfred P.
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p. 319 - 325
(2007/10/03)
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- Synthesis of D-Alloisoleucine from L-Isoleucine and from (S)-2-Methylbutan-1-ol. Synthesis of Isostatine
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Three different synthetic routes to the uncommon α-amino acid D-alloisoleucine were studied.The first was based on the stereospecific inversion of configuration of the C-2 stereogenic carbon of L-isoleucine.The second involved acetylation of L-isoleucine with epimerization at the C-2 carbon, giving a mixture of L-isoleucine and D-alloisoleucine, which was resolved enzymically with hog kidney acylase.In a new approach, an epimeric mixture of L-isoleucine and D-alloisoleucine was synthesized from (S)-2-methylbutan-1-ol and was again resolved enzymically.The D-alloisoleucine produced in these syntheses was subsequently transformed into the γ-amino acid isostatine.
- Lloyd-Williams, Paul,Monerris, Patricia,Gonzalez, Isabel,Jou, Gemma,Giralt, Ernest
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p. 1969 - 1974
(2007/10/02)
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- Synthesis of (2S,3S)-2-amino-3-methylpent-4-ynoic Acid, a Precursor Amino Acid for the Preparation of Tritium- or Deuterium-Labelled Peptide in the Isoleucine Residue
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The synthesis of (2S,3S)-2-amino-3-methylpent-4-ynoic acid (Amp) 1, its incorporation into a peptide chain, and the preparation of a deuterium-labelled peptide in the isoleucine residue are reported.Amino acid 1 was synthesized in three steps from 3-chlorobut-1-yne.The optical purity of amino acid 1 was determined by HPLC with a chiral stationary-phase column and was found to be more than 99percent (ee).Tyr-Amp-Leu was synthesized by solid-phase synthesis based on Fmoc strategy.The tripeptide was deuteriated catalytically to yield Tyr-Ile-Leu.The distribution of deuterium was investigated by fast-atom-bombardment mass spectrometry (FAB-MS) and (13)C NMR spectroscopy, which confirmed that the deuterium was located entirely at the isoleucine residue.
- Hasegawa, Hiroshi,Arai, Shinichi,Shinohara, Yoshihiko,Baba, Shigeo
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p. 489 - 494
(2007/10/02)
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- Acetylation under ultrasonic conditions: Convenient preparation of N-acetylamino acids
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An efficient and simple method of preparation of acetylamino acids from amino acids under ultrasonic conditions is described. The reactions proceed without racemization and the yields are almost quantitative.
- Veera Reddy,Ravindranath
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p. 257 - 264
(2007/10/02)
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- Syngas reactions XIV. Amidocarbonylation as a route to α-amidocarboxylic acids
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The amidocarbonylation of olefin and aldehyde substrates has been applied to the synthesis of a variety of amidocarboxylic acids, including surface active agents (e.g.C14-C16 N-acyl-α-amino acids), specialty surfactants (such as the sarcosinates), intermediates for sweeteners (e.g. aspartame), food additives (e.g. glutamic acid), and certain chelating agents.Homogeneous cobalt and rhodium-based catalysts, modified, for example, with sulfoxide and bidentate phosphine ligands, have been tailored to the synthesis of each individual class of product.Process studies, including examinations of reaction rate, product selectivity, as well as catalyst stability, have been undertaken for N-acetylglycine and amido acid surfactant syntheses.
- Lin, J.J.,Knifton, John F.
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- ENANTIOSELECTIVE HYDROLYSIS BY BAKER'S YEAST
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Optically active N-acetylamino acid esters were obtained by enantioselective hydrolysis of their racemates using fermenting baker's yeast.
- Glaenzer, B.I.,Faber, K.,Griengl, H.
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p. 4293 - 4294
(2007/10/02)
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