How to cite this WIREs title:
WIREs Comput Mol Sci

Impact Factor: 25.113

Rationalization of stereoselectivity in enzyme reactions

Advanced Review

H. C. Stephen Chan, Lu Pan, Yi Li, Shuguang Yuan

Published Online: Dec 05 2018

DOI: 10.1002/wcms.1403

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Enzymes are responsible for more than 5,000 different types of biochemical reactions. Enzymes speed up various chemical reactions in cell that would otherwise take millions of years to occur in milliseconds. The ability to discriminate between optical isomers is vital for living systems. The selective formation of only one product stereoisomer from achiral substrates is one of the most sophisticated tasks for enzymes. Because of the importance of stereoselectivity in biology, the structural and mechanistic basis underlying these phenomena has become the subject of intensive research. Enzymatic reactions provide the basis of cellular biochemistry and typically display high stereoselectivity. With the advances of enzyme engineering, in vitro evolution and, especially, computational rational design, scientists start to provide various methods and tools to manipulate the stereoselective properties of enzymes. To gain an insightful view of stereoselectivity in enzyme reactions, we present an extensive discussion on the latest progresses in this area. This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Structure and Mechanism > Reaction Mechanisms and Catalysis Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods

Scheme of enzyme catalysis. (a) The catalytic process and induced fit effect of enzyme. (b) The activation energy of enzyme catalysis compared to that of no enzyme reactions

[ Normal View | Magnified View ]

Calculated activation energy barrier and substrate−water distances of LEH variant SZ719. (a) The catalysis scheme of LEH. (b) The activation energy barrier of SZ719–CYO1. Distance in blue was calculated by QM methods. (c) Distances of C1O2 and C2O2 along MD simulations of SZ719–CYO1. (d) The activation energy barrier of SZ719–CYO3. Distance in blue was calculated by QM methods. (e) Distances of C1O2 and C2O2 along MD simulations of SZ719–CYO3. (Reprinted with permission from Reference . Copyright 2018 American Chemical Society)

[ Normal View | Magnified View ]

Two dominant binding modes of fluoroacetate dehalogenases (FAcD) substrates and their relative ligand binding energies. (a) The reaction scheme of FAcD. (b) The binding mode 1 of (S)‐1, with ΔG_S1 = −60.1 ± 1.1 kcal/mol (−35.4 ± 0.7, monomer). (c) The binding mode 2 of (S)‐1, with ΔG_S2 = −28.1 ± 0.4 kcal/mol (−14.4 ± 0.9, monomer). (d) The binding mode 1 of (R)‐1, with ΔG_R1 = −35.7 ± 0.7 kcal/mol (−16.4 ± 0.8, monomer). (e) The binding mode 2 of (R)‐1, with ΔG_S2 = −17.5 ± 1.1 kcal/mol (−6.4 ± 0.9, monomer). (Reprinted with permission from Reference . Copyright 2017 American Chemical Society)

[ Normal View | Magnified View ]

One‐pot consecutive two‐enzyme sequential cascade. 4‐Oxo‐pentenoate derivatives are first hydrogenated 4‐oxo‐pentanoate via enoate reductase (ER). The cis‐ or trans‐ of the precursors affect the anti‐ or syn‐configurations of the immediate products. The ketone is further reduced to hydroxyl group via alcohol dehydrogenase (ADH). ADH produced from various bacterial species such as Thermoanaerobacter sp. (ADH_T) or Lactobacillus brevis (ADH_LK) stereoselectively produces the alcohol semiproducts. The closure of lactone ring is achieved by simple acidification

[ Normal View | Magnified View ]

Engineering of CYP260A1 for stereoselective hydroxylation of progesterone. (a) S276 in the engineered enzyme corresponds to S326 in the native CYP260A1. S276I and S276N mutants selectively catalyze 1α‐ and 17α‐hydroxylation, respectively. (b) The binding mode of progesterone in S276I‐progesterone complex (PDB ID: 6F8C) corresponds to the predicted docking pose I. (c) The binding mode of progesterone in S276N‐progesterone complex (PDB ID: 6F88) corresponds to the predicted docking pose II

[ Normal View | Magnified View ]

Diels–Alder reaction. (a) The de novo designed diels‐alderase, DA_20_10, catalyzes the formation of nearly pure 3R,4S‐product. (b) True catalysis by ribozyme: the oligo(ethylene glycol) anthracene derivatives enters the active site via a wider opening. The resulting orientation favors the formation of R,R‐product. (c) Tethered catalysis: the anthracene moiety is tethered near the narrower backdoor openings on the ribozyme. A short ethylene glycol tether of 2–8 units long forces the substrate to enter the active site with opposite orientation, leading to S,S‐product

[ Normal View | Magnified View ]

References

Geng, J, Yao, C, Kou, X, Tang, J, Luo, D, Yang, D. A fluorescent biofunctional DNA hydrogel prepared by enzymatic polymerization. Adv Healthc Mater. 2017;7:1700998.
Ciric‐Marjanovic, G, Milojevic‐Rakic, M, Janosevic‐Lezaic, A, Luginbuhl, S, Walde, P. Enzymatic oligomerization and polymerization of arylamines: State of the art and perspectives. Chem Zvesti. 2017;71:199–242.
Satoh, K, Kamigaito, M. Stereospecific living radical polymerization: Dual control of chain length and tacticity for precision polymer synthesis. Chem Rev. 2009;109:5120–5156.
Moura, M, Finkle, J, Stainbrook, S, Greene, J, Broadbelt, LJ, Tyo, KEJ. Evaluating enzymatic synthesis of small molecule drugs. Metab Eng. 2016;33:138–147.
Metzner, R, Hummel, W, Wetterich, F, König, B, Gröger, H. Integrated biocatalysis in multistep drug synthesis without intermediate isolation: A de novo approach toward a Rosuvastatin key building block. Org Process Res Dev. 2015;19:635–638.
Shoda, S, Uyama, H, Kadokawa, J, Kimura, S, Kobayashi, S. Enzymes as green catalysts for precision macromolecular synthesis. Chem Rev. 2016;116:2307–2413.
Robinson, PK. Enzymes: Principles and biotechnological applications. Essays Biochem. 2015;59:1–41.
Kobayashi, S. New developments of polysaccharide synthesis via enzymatic polymerization. Proc Jpn Acad Ser B Phys Biol Sci. 2007;83:215–247.
Sherman, W, Day, T, Jacobson, MP, Friesner, RA, Farid, R. Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem. 2006;49:534–553.
Poshyvailo, L, von Lieres, E, Kondrat, S. Does metabolite channeling accelerate enzyme‐catalyzed cascade reactions? PLoS One. 2017;12:e0172673.
Schomburg, I, Chang, A, Placzek, S, et al. BRENDA in 2013: Integrated reactions, kinetic data, enzyme function data, improved disease classification: New options and contents in BRENDA. Nucleic Acids Res. 2013;41:D764–D772.
Mifsud, M, Gargiulo, S, Iborra, S, Arends, IW, Hollmann, F, Corma, A. Photobiocatalytic chemistry of oxidoreductases using water as the electron donor. Nat Commun. 2014;5:3145.
Ngoka, LC. Dramatic down‐regulation of oxidoreductases in human hepatocellular carcinoma hepG2 cells: Proteomics and gene ontology unveiling new frontiers in cancer enzymology. Proteome Sci. 2008;6:29.
Wagner, AM, Fegley, MW, Warner, JB, Grindley, CL, Marotta, NP, Petersson, EJ. N‐terminal protein modification using simple aminoacyl transferase substrates. J Am Chem Soc. 2011;133:15139–15147.
Jongkees, SA, Withers, SG. Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases. J Am Chem Soc. 2011;133:19334–19337.
Chambers, KA, Abularrage, NS, Scheck, RA. Selectivity within a family of bacterial phosphothreonine lyases. Biochemistry. 2018;57:3790–3796.
Li, Q, Qin, X, Liu, J, et al. Deciphering the biosynthetic origin of l‐allo‐isoleucine. J Am Chem Soc. 2016;138:408–415.
Cohen, JD, Thompson, S, Ting, AY. Structure‐guided engineering of a Pacific Blue fluorophore ligase for specific protein imaging in living cells. Biochemistry. 2011;50:8221–8225.
Hutt, AG, O`Grady, J. Drug chirality: A consideration of the significance of the stereochemistry of antimicrobial agents. J Antimicrob Chemother. 1996;37:7–32.
Nguyen, LA, He, H, Pham‐Huy, C. Chiral drugs: An overview. Int J Biomed Sci. 2006;2:85–100.
Pearson, AA, Gaffney, TE, Walle, T, Privitera, PJ. A stereoselective central hypotensive action of atenolol. J Pharmacol Exp Ther. 1989;250:759–763.
Stoschitzky, K, Egginger, G, Zernig, G, Klein, W, Lindner, W. Stereoselective features of (R)‐ and (S)‐atenolol: Clinical pharmacological, pharmacokinetic, and radioligand binding studies. Chirality. 1993;5:15–19.
Shi, W, Nacev, BA, Bhat, S, Liu, JO. Impact of absolute stereochemistry on the antiangiogenic and antifungal activities of Itraconazole. ACS Med Chem Lett. 2010;1:155–159.
Kunze, KL, Nelson, WL, Kharasch, ED, Thummel, KE, Isoherranen, N. Stereochemical aspects of itraconazole metabolism in vitro and in vivo. Drug Metab Dispos. 2006;34:583–590.
Teo, SK, Colburn, WA, Tracewell, WG, et al. Clinical pharmacokinetics of thalidomide. Clin Pharmacokinet. 2004;43:311–327.
Eriksson, T, Bjorkman, S, Roth, B, Fyge, A, Hoglund, P. Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide. Chirality. 1995;7:44–52.
Siegel, JB, Zanghellini, A, Lovick, HM, et al. Computational design of an enzyme catalyst for a stereoselective bimolecular Diels‐Alder reaction. Science. 2010;329:309–313.
Kuhlman, B, Baker, D. Native protein sequences are close to optimal for their structures. Proc Natl Acad Sci U S A. 2000;97:10383–10388.
Lu, P, Min, D, DiMaio, F, et al. Accurate computational design of multipass transmembrane proteins. Science. 2018;359:1042–1046.
Classen, T, Korpak, M, Schölzel, M, Pietruszka, J. Stereoselective enzyme cascades: An efficient synthesis of chiral γ‐butyrolactones. ACS Catal. 2014;4:1321–1331.
Minami, A, Oikawa, H. Recent advances of Diels‐Alderases involved in natural product biosynthesis. J Antibiot (Tokyo). 2016;69:500–506.
Zanghellini, A, Jiang, L, Wollacott, AM, et al. New algorithms and an in silico benchmark for computational enzyme design. Protein Sci. 2006;15:2785–2794.
Dou, J, Vorobieva, AA, Sheffler, W, et al. De novo design of a fluorescence‐activating beta‐barrel. Nature. 2018;561:485–491.
Szaleniec, M, Wojtkiewicz, AM, Bernhard, R, Borowski, T, Donova, M. Bacterial steroid hydroxylases: Enzyme classes, their functions and comparison of their catalytic mechanisms. Appl Microbiol Biotechnol. 2018;102:8153–8171.
Khatri, Y, Jozwik, IK, Ringle, M, et al. Structure‐based engineering of steroidogenic CYP260A1 for stereo‐ and regioselective hydroxylation of progesterone. ACS Chem Biol. 2018;13:1021–1028.
Trott, O, Olson, AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455–461.
Reetz, MT. Laboratory evolution of stereoselective enzymes: A prolific source of catalysts for asymmetric reactions. Angew Chem Int Ed Engl. 2011;50:138–174.
Huang, WC, Cullis, PM, Raven, EL, Roberts, GC. Control of the stereo‐selectivity of styrene epoxidation by cytochrome P450 BM3 using structure‐based mutagenesis. Metallomics. 2011;3:410–416.
Jones, G, Willett, P, Glen, RC, Leach, AR, Taylor, R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol. 1997;267:727–748.
Chan, HCS, Wang, J, Palczewski, K, et al. Exploring a new ligand binding site of G protein‐coupled receptors. Chem Sci. 2018;9:6480–6489.
Li, G, Maria‐Solano, MA, Romero‐Rivera, A, Osuna, S, Reetz, MT. Inducing high activity of a thermophilic enzyme at ambient temperatures by directed evolution. Chem Commun (Camb). 2017;53:9454–9457.
Dodani, SC, Kiss, G, Cahn, JK, Su, Y, Pande, VS, Arnold, FH. Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models. Nat Chem. 2016;8:419–425.
Wombacher, R, Keiper, S, Suhm, S, Serganov, A, Patel, DJ, Jaschke, A. Control of stereoselectivity in an enzymatic reaction by backdoor access. Angew Chem Int Ed Engl. 2006;45:2469–2472.
Morris, GM, Huey, R, Lindstrom, W, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009;30:2785–2791.
Heinisch, T, Ward, TR. Artificial metalloenzymes based on the biotin‐streptavidin technology: Challenges and opportunities. Acc Chem Res. 2016;49:1711–1721.
Kohler, V, Wilson, YM, Durrenberger, M, et al. Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes. Nat Chem. 2013;5:93–99.
Li, G, Reetz, MT. Learning lessons from directed evolution of stereoselective enzymes. Org Chem Front. 2016;3:1350–1358.
Hammer, SC, Knight, AM, Arnold, FH. Design and evolution of enzymes for non‐natural chemistry. Curr Opin Green Sustain Chem. 2017;7:23–30.
Arnold, FH. Directed evolution: Bringing new chemistry to life. Angew Chem Int Ed Engl. 2018;57:4143–4148.
Kan, SB, Lewis, RD, Chen, K, Arnold, FH. Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life. Science. 2016;354:1048–1051.
Kan, SBJ, Huang, X, Gumulya, Y, Chen, K, Arnold, FH. Genetically programmed chiral organoborane synthesis. Nature. 2017;552:132–136.
Vischer, HF, Vink, C, Smit, MJ. A viral conspiracy: Hijacking the chemokine system through virally encoded pirated chemokine receptors. Curr Top Microbiol Immunol. 2006;303:121–154.
Reetz, MT, Carballeira, JD. Iterative saturation mutagenesis (ISM) for rapid directed evolution of functional enzymes. Nat Protoc. 2007;2:891–903.
Reetz, MT, Bocola, M, Carballeira, JD, Zha, D, Vogel, A. Expanding the range of substrate acceptance of enzymes: Combinatorial active‐site saturation test. Angew Chem Int Ed Engl. 2005;44:4192–4196.
Patrick, WM, Firth, AE. Strategies and computational tools for improving randomized protein libraries. Biomol Eng. 2005;22:105–112.
Sun, Z, Wikmark, Y, Backvall, JE, Reetz, MT. New concepts for increasing the efficiency in directed evolution of stereoselective enzymes. Chemistry. 2016;22:5046–5054.
Sun, Z, Lonsdale, R, Wu, L, et al. Structure‐guided triple‐code saturation mutagenesis: Efficient tuning of the stereoselectivity of an epoxide hydrolase. ACS Catal. 2016;6:1590–1597.
Tinoco, A, Steck, V, Tyagi, V, Fasan, R. Highly diastereo‐ and enantioselective synthesis of trifluoromethyl‐substituted cyclopropanes via myoglobin‐catalyzed transfer of trifluoromethylcarbene. J Am Chem Soc. 2017;139:5293–5296.
Bajaj, P, Sreenilayam, G, Tyagi, V, Fasan, R. Gram‐scale synthesis of chiral cyclopropane‐containing drugs and drug precursors with engineered myoglobin catalysts featuring complementary stereoselectivity. Angew Chem Int Ed Engl. 2016;55:16110–16114.
Schwizer, F, Okamoto, Y, Heinisch, T, et al. Artificial metalloenzymes: Reaction scope and optimization strategies. Chem Rev. 2018;118:142–231.
Key, HM, Dydio, P, Clark, DS, Hartwig, JF. Abiological catalysis by artificial haem proteins containing noble metals in place of iron. Nature. 2016;534:534–537.
Dydio, P, Key, HM, Nazarenko, A, et al. An artificial metalloenzyme with the kinetics of native enzymes. Science. 2016;354:102–106.
Jeschek, M, Reuter, R, Heinisch, T, et al. Directed evolution of artificial metalloenzymes for in vivo metathesis. Nature. 2016;537:661–665.
Hestericova, M, Heinisch, T, Alonso‐Cotchico, L, Marechal, JD, Vidossich, P, Ward, TR. Directed evolution of an artificial imine reductase. Angew Chem Int Ed Engl. 2018;57:1863–1868.
Wang, L, Berne, BJ, Friesner, RA. On achieving high accuracy and reliability in the calculation of relative protein–ligand binding affinities. Proc Natl Acad Sci U S A. 2012;109:1937–1942.
Gilson, MK, Zhou, HX. Calculation of protein–ligand binding affinities. Annu Rev Biophys Biomol Struct. 2007;36:21–42.
Maguire, JJ, Kuc, RE, Davenport, AP. Radioligand binding assays and their analysis. Methods Mol Biol. 2012;897:31–77.
Hulme, EC, Trevethick, MA. Ligand binding assays at equilibrium: Validation and interpretation. Br J Pharmacol. 2010;161:1219–1237.
Mould, R, Brown, J, Marshall, FH, Langmead, CJ. Binding kinetics differentiates functional antagonism of orexin‐2 receptor ligands. Br J Pharmacol. 2014;171:351–363.
Andersen, ME, Moffat, JK, Gibson, QH. The kinetics of ligand binding and of the association–dissociation reactions of human hemoglobin. Properties of deoxyhemoglobin dimers. J Biol Chem. 1971;246:2796–2807.
Dong, C, Liu, Z, Wang, F. Radioligand saturation binding for quantitative analysis of ligand–receptor interactions. Biophys Rep. 2015;1:148–155.
Feau, C, Arnold, LA, Kosinski, A, Guy, RK. A high‐throughput ligand competition binding assay for the androgen receptor and other nuclear receptors. J Biomol Screen. 2009;14:43–48.
Zhai, D, Godoi, P, Sergienko, E, et al. High‐throughput fluorescence polarization assay for chemical library screening against anti‐apoptotic Bcl‐2 family member Bfl‐1. J Biomol Screen. 2012;17:350–360.
Lea, WA, Simeonov, A. Fluorescence polarization assays in small molecule screening. Expert Opin Drug Discovery. 2011;6:17–32.
Sekar, RB, Periasamy, A. Fluorescence resonance energy transfer (FRET) microscopy imaging of live cell protein localizations. J Cell Biol. 2003;160:629–633.
Tang, Y, Zeng, X, Liang, J. Surface plasmon resonance: An introduction to a surface spectroscopy technique. J Chem Educ. 2010;87:742–746.
Chavanieu, A, Pugniere, M. Developments in SPR fragment screening. Expert Opin Drug Discovery. 2016;11:489–499.
Genheden, S, Ryde, U. The MM/PBSA and MM/GBSA methods to estimate ligand‐binding affinities. Expert Opin Drug Discovery. 2015;10:449–461.
Jorgensen, WL, Thomas, LL. Perspective on free‐energy perturbation calculations for chemical equilibria. J Chem Theory Comput. 2008;4:869–876.
Ruiter, A, Oostenbrink, C. Extended thermodynamic integration: Efficient prediction of lambda derivatives at nonsimulated points. J Chem Theory Comput. 2016;12:4476–4486.
Wang, JB, Ilie, A, Yuan, S, Reetz, MT. Investigating substrate scope and enantioselectivity of a defluorinase by a stereochemical probe. J Am Chem Soc. 2017;139:11241–11247.
Sun, Z, Wu, L, Bocola, M, et al. Structural and computational insight into the catalytic mechanism of limonene epoxide hydrolase mutants in stereoselective transformations. J Am Chem Soc. 2018;140:310–318.
Liao, RZ, Siegbahn, PEM. Mechanism and selectivity of the dinuclear iron benzoyl‐coenzyme A epoxidase BoxB. Chem Sci. 2015;6:2754–2764.
Noey, EL, Tibrewal, N, Jimenez‐Oses, G, et al. Origins of stereoselectivity in evolved ketoreductases. Proc Natl Acad Sci U S A. 2015;112:E7065–E7072.
Yuan, H, Zhang, J, Cai, Y, et al. GyrI‐like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection. Nat Commun. 2017;8:1485.
Mehvar, R, Brocks, DR. Stereospecific pharmacokinetics and pharmacodynamics of beta‐adrenergic blockers in humans. J Pharm Pharm Sci. 2001;4:185–200.
Lukša, J, Josić, D, Podobnik, B, Furlan, B, Kremser, M. Semi‐preparative chromatographic purification of the enantiomers S‐(−)‐amlodipine and R‐(+)‐amlodipine. J Chromatogr B Biomed Sci Appl. 1997;693:367–375.
Antonaccio, MJ. Angiotensin converting enzyme (ACE) inhibitors. Annu Rev Pharmacol Toxicol. 1982;22:57–87.
Flesch, G, Müller, P, Lloyd, P. Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin Pharmacol. 1997;52:115–120.
Landoni, MF, Soraci, A. Pharmacology of chiral compounds 2‐arylpropionic acid derivatives. Curr Drug Metab. 2001;2:37–51.
Brossi, A, Pei, X‐F. Biological activity of unnatural alkaloid enantiomers. In: Cordell, GA, editor. The alkaloids: Chemistry and biology. Volume 50. Academic Press, 1998; p. 109–139.
Mitra, S, Chopra, P. Chirality and anaesthetic drugs: A review and an update. Indian J Anaesth. 2011;55:556–562.
Gascon, AR, Campo, E, Hernandez, RM, Calvo, B, Errasti, J, Pedraz Munoz, JL. Pharmacokinetics of ofloxacin enantiomers after intravenous administration for antibiotic prophylaxis in biliary surgery. J Clin Pharmacol. 2000;40:869–874.
Weinberg, ED, Tonnis, SM. Action of chloramphenicol and its isomers on secondary biosynthetic processes of bacillus. Appl Microbiol. 1966;14:850–856.
Korhonova, M, Doricakova, A, Dvorak, Z. Optical isomers of atorvastatin, rosuvastatin and fluvastatin enantiospecifically activate Pregnane X receptor PXR and induce CYP2A6, CYP2B6 and CYP3A4 in human hepatocytes. PLoS One. 2015;10:e0137720.
Dinis‐Oliveira, RJ. Metabolic profile of oxazepam and related benzodiazepines: Clinical and forensic aspects. Drug Metab Rev. 2017;49:451–463.
Greenblatt, DJ, Zammit, GK. Pharmacokinetic evaluation of eszopiclone: Clinical and therapeutic implications. Expert Opin Drug Metab Toxicol. 2012;8:1609–1618.
Blake, K, Raissy, H. Chiral switch drugs for asthma and allergies: True benefit or marketing hype. Pediatr Allergy Immunol Pulmonol. 2013;26:157–160.
Jeon, SH, Kim, M, Han, HK, Lee, W. Direct enantiomer separation of thyroxine in pharmaceuticals using crown ether type chiral stationary phase. Arch Pharm Res. 2010;33:1419–1423.

Further Reading

Antonaccio, MJ. Angiotensin converting enzyme (ACE) inhibitors. Annu Rev Pharmacol Toxicol. 1982;22:57–87.
Blake, K, Raissy, H. Chiral switch drugs for asthma and allergies: True benefit or marketing hype. Pediatr Allergy Immunol Pulmonol. 2013;26:157–160.
Brossi, A, Pei, X‐F. Biological activity of unnatural alkaloid enantiomers. In: Cordell, GA, editor. The alkaloids: Chemistry and biology. Volume 50. Academic Press, 1998; p. 109–139.
Dinis‐Oliveira, RJ. Metabolic profile of oxazepam and related benzodiazepines: Clinical and forensic aspects. Drug Metab Rev. 2017;49:451–463.
Flesch, G, Müller, P, Lloyd, P. Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin Pharmacol. 1997;52:115–120.
Gascon, AR, Campo, E, Hernandez, RM, Calvo, B, Errasti, J, Pedraz Munoz, JL. Pharmacokinetics of ofloxacin enantiomers after intravenous administration for antibiotic prophylaxis in biliary surgery. J Clin Pharmacol. 2000;40:869–874.
Greenblatt, DJ, Zammit, GK. Pharmacokinetic evaluation of eszopiclone: Clinical and therapeutic implications. Expert Opin Drug Metab Toxicol. 2012;8:1609–1618.
Jeon, SH, Kim, M, Han, HK, Lee, W. Direct enantiomer separation of thyroxine in pharmaceuticals using crown ether type chiral stationary phase. Arch Pharm Res. 2010;33:1419–1423.
Korhonova, M, Doricakova, A, Dvorak, Z. Optical isomers of atorvastatin, rosuvastatin and fluvastatin enantiospecifically activate Pregnane X receptor PXR and induce CYP2A6, CYP2B6 and CYP3A4 in human hepatocytes. PLoS One. 2015;10:e0137720.
Landoni, MF, Soraci, A. Pharmacology of chiral compounds 2‐arylpropionic acid derivatives. Curr Drug Metab. 2001;2:37–51.
Lukša, J, Josić, D, Podobnik, B, Furlan, B, Kremser, M. Semi‐preparative chromatographic purification of the enantiomers S‐(−)‐amlodipine and R‐(+)‐amlodipine. J Chromatogr B Biomed Sci Appl. 1997;693:367–375.
Mehvar, R, Brocks, DR. Stereospecific pharmacokinetics and pharmacodynamics of beta‐adrenergic blockers in humans. J Pharm Pharm Sci. 2001;4:185–200.
Mitra, S, Chopra, P. Chirality and anaesthetic drugs: A review and an update. Indian J Anaesth. 2011;55:556–562.
Weinberg, ED, Tonnis, SM. Action of chloramphenicol and its isomers on secondary biosynthetic processes of bacillus. Appl Microbiol. 1966;14:850–856.

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts