Dept. of Biochemistry & Organic Chemistry
Biosensor based interaction studies
A molecule in isolation has no function - but once it interacts with another molecule it can exhibit a variety of functions. Biomolecular interactions are often described on the basis of the molecules that interact, their individual structures and the structure of the complex. The kinetics, forces and energetics involved are more difficult to describe, although they are important for understanding the characteristics of the interaction. General, simple and accurate techniques for studying biomolecular interactions are not readily available. We have successfully exploited a surface plasmon based biosensor (Biacore) to study interactions between proteins and ligands. These studies provide detailed information about interactions and can for example be used for the design of new or improved drugs.
Our research has involved a variety of targets and ligands, analysis of compound libraries and extraction of detailed data that has been used to determine the kinetics, chemodynamics and thermodynamics of the interactions.
Selected publications
- Geitmann M, Unge T, Danielson UH. Interaction kinetic characterization of HIV-1 reverse transcriptase non-nucleoside inhibitor resistance.
J Med Chem. 2006 Apr 20;49(8):2375-87. - Geitmann M, Unge T, Danielson UH. Biosensor-based kinetic characterization of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors.
J Med Chem. 2006 Apr 20;49(8):2367-74. - Backman D, Monod M, Danielson UH. Biosensor-based screening and characterization of HIV-1 inhibitor interactions with Sap 1, Sap 2, and Sap 3 from Candida albicans.
J Biomol Screen. 2006 Mar;11(2):165-75. - Cimitan S, Lindgren MT, Bertucci C, Danielson UH. Early absorption and distribution analysis of antitumor and anti-AIDS drugs: lipid membrane and plasma protein interactions.
J Med Chem. 2005 May 19;48(10):3536-46. - Shuman CF, Vrang L, Danielson UH. Improved structure-activity relationship analysis of HIV-1 protease inhibitors using interaction kinetic data.
J Med Chem. 2004 Nov 18;47(24):5953-61. - Geitmann M, Danielson UH. Studies of substrate-induced conformational changes in human cytomegalovirus protease using optical biosensor technology.
Anal Biochem. 2004 Sep 15;332(2):203-14. - Shuman CF, Hamalainen MD, Danielson UH. Kinetic and thermodynamic characterization of HIV-1 protease inhibitors.
J Mol Recognit. 2004 Mar-Apr;17(2):106-19. - Gossas T, Danielson UH. Analysis of the pH-dependencies of the association and dissociation kinetics of HIV-1 protease inhibitors.
J Mol Recognit. 2003 Jul-Aug;16(4):203-12. - Shuman CF, Markgren PO, Hamalainen M, Danielson UH. Elucidation of HIV-1 protease resistance by characterization of interaction kinetics between inhibitors and enzyme variants.
Antiviral Res. 2003 May;58(3):235-42. - Backman D, Danielson UH. Kinetic and mechanistic analysis of the association and dissociation of inhibitors interacting with secreted aspartic acid proteases 1 and 2 from Candida albicans.
Biochim Biophys Acta. 2003 Mar 21;1646(1-2):184-95. - Markgren PO, Schaal W, Hamalainen M, Karlen A, Hallberg A, Samuelsson B, Danielson UH. Relationships between structure and interaction kinetics for HIV-1 protease inhibitors.
J Med Chem. 2002 Dec 5;45(25):5430-9. - Markgren PO, Lindgren MT, Gertow K, Karlsson R, Hamalainen M, Danielson UH. Determination of interaction kinetic constants for HIV-1 protease inhibitors using optical biosensor technology.
Anal Biochem. 2001 Apr 15;291(2):207-18. - Alterman M, Sjobom H, Safsten P, Markgren PO, Danielson UH, Hamalainen M, Lofas S, Hulten J, Classon B, Samuelsson B, Hallberg A. P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays.
Eur J Pharm Sci. 2001 May;13(2):203-12. - Hamalainen MD, Markgren PO, Schaal W, Karlen A, Classon B, Vrang L, Samuelsson B, Hallberg A, Danielson UH. Characterization of a set of HIV-1 protease inhibitors using binding kinetics data from a biosensor-based screen.
J Biomol Screen. 2000 Oct;5(5):353-60. - Markgren PO, Hamalainen M, Danielson UH. Kinetic analysis of the interaction between HIV-1 protease and inhibitors using optical biosensor technology.
Anal Biochem. 2000 Mar 1;279(1):71-8. - Markgren PO, Hamalainen M, Danielson UH. Screening of compounds interacting with HIV-1 proteinase using optical biosensor technology.
Anal Biochem. 1998 Dec 15;265(2):340-50.