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P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. (Organic Pharmaceutical Chemistry)
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry.
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2001 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 13, no 2, 203-212 p.Article in journal (Refereed) Published
Abstract [en]

The commonly used HIV-1 protease assays rely on measurements of the effect of inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based on surface plasmon resonance (SPR) was introduced. We have taken advantage of the fact that the SPR signal is proportional to the mass of the analyte interacting with the immobilised molecule and developed two new improved efficient competition assay methods. Thus, high molecular weight binders were used as amplifiers of the surface plasmon resonance signal. Linkers were attached by a Heck reaction to the para-positions of the P1/P1′ benzyloxy groups of a linear C2-symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b) direct immobilisation of the inhibitor to the biosensor surface matrix. The interaction properties of a series of 17 structurally diverse inhibitors was assessed and compared to previously reported data. The most sensitive assay was obtained by immobilising the enzyme and amplifying the signal with an antibody, giving a detection range between 0.1 nM and 10 μM. Immobilisation of the inhibitor resulted in a stable and durable surface but a narrower detection range (1–100 nM). The two competition assays are anticipated to be very suitable for fast screening of potential HIV inhibitors.

Place, publisher, year, edition, pages
Elsevier , 2001. Vol. 13, no 2, 203-212 p.
Keyword [en]
HIV protease inhibitors, HIV protease, Screening, Surface plasmon resonance, Biosensor
National Category
Pharmaceutical Sciences Natural Sciences
URN: urn:nbn:se:uu:diva-51294DOI: 10.1016/S0928-0987(01)00109-9OAI: oai:DiVA.org:uu-51294DiVA: diva2:79203
Available from: 2006-03-04 Created: 2006-03-04 Last updated: 2010-07-19Bibliographically approved

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Alterman, MathiasMarkgren, Per-OlofDanielson, U. HelenaHultén, JohanHallberg, Anders
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Department of Medicinal ChemistryDepartment of Biochemistry
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