ABSTRACT
The use of halogen bond is widespread in drug discovery, design, and clinical trials, but is overlooked in drug biosynthesis. Here, the role of halogen bond in the nitrilase-catalyzed synthesis of ortho-, meta-, and para-chlorophenylacetic acid was investigated. Different distributions of halogen bond induced changes of substrate binding conformation and affected substrate selectivity. By engineering the halogen interaction, the substrate selectivity of the enzyme changed, with the implication that halogen bond plays an important role in biosynthesis and should be used as an efficient and reliable tool in enzymatic drug synthesis.
Subject(s)
Aminohydrolases/genetics , Aminohydrolases/metabolism , Halogens/chemistry , Phenylacetates/metabolism , Aminohydrolases/chemistry , Catalysis , Catalytic Domain , Drug Discovery , Models, Molecular , Molecular Conformation , Molecular Dynamics Simulation , Molecular Structure , Mutation , Phenylacetates/chemistry , Quantum Theory , Substrate SpecificityABSTRACT
AIM: To isolate and prepare chemical standards. METHODS: Flavonol glycoside and rhamnonic acid gamma-lactone were isolated from whole plants of Lysimachia christinae Hance. with 95% ethanol and purified by silica gel column chromatography. UV, IR, MS, 1HNMR, 13CNMR, DEPT, HMQC, HMBC were used for the structural identification. RESULTS: Two compounds were obtained. They were identified as rhamnonic acid gamma-lactone (I) and kaempferol-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-xyloside (II). CONCLUSION: Compound I was isolated from this genus for the first time. Compound II is a new compound named as lysimachiin.
