875-74-1Relevant articles and documents
Formation of Quasi-racemic Diastereoisomeric Salts as a Structural Cause for Efficient Optical Resolution
Fogassy, Elemer,Kozma, David
, p. 5069 - 5070 (1995)
During optical resolutions, when the resolving agent is structurally similar to the racemate, very efficient resolution can be achieved, because of the formation of quasi-racemic diastereoisomeric salts, in which the enantiomers have opposite configuration.
The Methyl Ester of α-Aminophenylacetic Acid: pH-Dependence and Phosphate Catalysis of Hydrolysis
Blinkovsky, Alexander M.,Galaev, Igor Yu.,Svedas, Vytas K.
, p. 1537 - 1540 (1986)
The dependence of the rate of spontaneous (non-enzymic) hydrolysis of α-aminophenylacetic acid methyl ester on the acidity of a medium was studied over the pH range 0.95-11.6.The mono- and dianion of phosphate was found to have a catalytic effect on this reaction, according to the mechanism of general base catalysis.Catalysis of the protonated substrate from hydrolysis by different phosphate ions, the second molecule of water, and the hydroxide ion follows the Broensted catalysis law with the slope 0.60.At a strong alkaline pH, phosphate slows down the ester hydrolysis, probably due to the formation of an ester-phosphate complex; the calculated dissociation constant is 4.2xE-3M, while the ratio of the hydrolysis rate constants for free ester and its phosphate complex is 7.7.
D-Phenylglycine aminotransferase (d-PhgAT)-substrate scope and structural insights of a stereo-inverting biocatalyst used in the preparation of aromatic amino acids
Akhtar, M. Kalim,Campopiano, Dominic J.,De Cesare, Silvia,Loake, Gary J.,Marles-Wright, Jon,Serpico, Annabel
, p. 6533 - 6543 (2020/11/13)
Enantiopure amines are key building blocks in the synthesis of many pharmaceuticals, so a route to their production is a current goal for biocatalysis. The stereo-inverting d-phenylglycine aminotransferase (d-PhgAT), isolated from Pseudomonas stutzeri ST-201, catalyses the reversible transamination from l-glutamic acid to benzoylformate, yielding α-ketoglutarate and d-phenylglycine (d-Phg). Detailed kinetic analysis revealed a range of amine donor and acceptor substrates that allowed the synthesis of enantiopure aromatic d-amino acids at a preparative scale. We also determined the first X-ray crystal structure of d-PhgAT with its bound pyridoxal 5′-phosphate (PLP) cofactor at 2.25 ? resolution. A combination of structural analysis and site-directed mutagenesis of this class III aminotransferase revealed key residues that are potentially involved in the dual substrate recognition, as well as controlling the stereo-inverting behaviour of d-PhgAT. Two arginine residues (Arg34 and Arg407) are involved in substrate recognition within P and O binding pockets respectively. These studies lay the foundation for further enzyme engineering and promote d-PhgAT as a useful biocatalyst for the sustainable production of high value, aromatic d-amino acids. This journal is
Deracemization and stereoinversion to aromatic d-amino acid derivatives with ancestral l-amino acid oxidase
Nakano, Shogo,Minamino, Yuki,Hasebe, Fumihito,Ito, Sohei
, p. 10152 - 10158 (2019/10/19)
Enantiomerically pure amino acid derivatives could be foundational compounds for peptide drugs. Deracemization of racemates to l-amino acid derivatives can be achieved through the reaction of evolved d-amino acid oxidase and chemical reductants, whereas deracemization to d-amino acid derivatives has not progressed due to the difficulty associated with the heterologous expression of l-amino acid oxidase (LAAO). In this study, we succeeded in developing an ancestral LAAO (AncLAAO) bearing broad substrate selectivity (13 l-amino acids) and high productivity through an Escherichia coli expression system (50.7 mg/L). AncLAAO can be applied to perform deracemization to d-amino acids in a similar way to deracemization to l-amino acids. In fact, full conversion (>99% ee, d-form) could be achieved for 16 racemates, including nine d,l-Phe derivatives, six d,l-Trp derivatives, and a d,l-phenylglycine. Taken together, we believe that AncLAAO could be a key enzyme to obtain optically pure d-amino acid derivatives in the future.