Abstract
The three-dimensional shape of a molecule has a decisive influence on its biological activity. The configuration of a molecule is made up of the bonds between the atoms. Substances with an asymmetric center that are considered here are optically active and exist in two different forms. They are asymmetrically built and have a relationship to one another like of an image and its mirror image. They are called chiral. It is impossible to convert one form into the other without breaking and remaking bonds. Chirality is often unimportant to a chemist because the image and mirror image behave exactly the same in a symmetrical environment. If they are brought into an asymmetrical environment, for instance at the binding site of a protein, that is not true anymore. The consequences of this for drug design and therapy are the topic of this chapter.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Bibliography
General Literature
Ariëns EJ, Soudijn W, Timmermans PBMWM (1983) Stereochemistry and biological activity of drugs. Blackwell Scientific, Oxford
Brown C (ed) (1990) Chirality in drug design and synthesis. Academic, London
Caner H, Groner E, Levy L (2004) Trends in the development of chiral drugs. Drug Discov Today 9:105–110
Eichelbaum M, Testa B, Somogyi A (2002) Handbook of experimental pharmacology, stereochemical aspects of drug action and disposition. Springer, Heidelberg
Holmstedt B, Frank H, Testa B (1990) Chirality and biological activity. Alan R. Liss, New York
Klebe G (2004) Differences in binding of stereoisomers to protein active sites. In: Pifat-Mrzljak G (ed) Supramolecular structure and function 8. Kluwer Academic/Plenum, New York, pp 31–53
Smith DF (ed) (1989) CRC handbook of stereoisomers: therapeutic drugs. CRC Press, Boca Raton
Special Literature
Ariëns EJ (1984) Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur J Clin Pharmacol 26:663–668
Ariëns EJ (1993) Nonchiral, homochiral and composite chiral drugs. Trends Pharmacol Sci 14:68–75
Ariëns EJ et al (1976) Stereoselectivity and affinity in molecular pharmacology. Fortschr Arzneimittelforsch 20:101–142
Bocola M, Stubbs MT, Sotriffer C, Hauer B, Friedrich T, Dittrich K, Klebe G (2003) Structural and energetic determinants for enantiopreferences in kinetic resolution of lipases. Protein Eng 16:319–322
Greer J, Erickson JW, Baldwin JJ, Varney MD (1994) Application of the three-dimensional structures of protein target molecules in structure-based drug design. J Med Chem 37:1035–1054
Jung G (1992) Proteins from the d-chiral world. Angew Chem Int Ed Engl 31:1457–1459
Klaholz BP, Mitschler A, Belema M, Zusi C, Moras D (2002) Enantiomer discrimination illustrated by high-resolution crystal structures of the human nuclear receptor hRARγ. Proc Natl Acad Sci USA 97:6322–6327
Mason S (1986) The origin of chirality in nature. Trends Pharmacol Sci 7: 20–23, and other articles from the same author on pp. 60–64, 112–116, 155–158, 200–205, 227–230 and 281–285
Stinson SC (1994) Chiral drugs. Chem Eng News S. 38–72, and 9 Oct 1995, S. 44–74
Stubbs MT, Huber R, Bode W (1995) Crystal structures of factor Xa-specific Inhibitors in complex with Trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin. FEBS Lett 375:103–107
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Klebe, G. (2013). Optical Activity and Biological Effect. In: Klebe, G. (eds) Drug Design. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17907-5_5
Download citation
DOI: https://doi.org/10.1007/978-3-642-17907-5_5
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-17906-8
Online ISBN: 978-3-642-17907-5
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences
