Influence of azide incorporation on binding affinity by small papain inhibitors
| Autor: | Floris L. van Delft, Marloes A. Wijdeven, Jan C. M. van Hest, Floris P. J. T. Rutjes, Helene I. V. Amatdjais-Groenen, Angelique E. M. Wammes, Tina Ritschel, Tom Hendriks |
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| Rok vydání: | 2014 |
| Předmět: |
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Molecular Azides Stereochemistry Clinical Biochemistry Pharmaceutical Science Synthetic Organic Chemistry Cysteine Proteinase Inhibitors Ligands Bio-Organic Chemistry Biochemistry Small Molecule Libraries chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Papain Moiety Molecular Biology Binding Sites Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Cycloaddition Alkynes Molecular Medicine Azide Biosensor Linker Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] |
| Zdroj: | Bioorganic & Medicinal Chemistry, 22, 5593-603 Bioorganic & Medicinal Chemistry, 22, 20, pp. 5593-603 Bioorganic & Medicinal Chemistry, 22, 5593-5603 Bioorganic & Medicinal Chemistry, 22, 20, pp. 5593-5603 |
| ISSN: | 0968-0896 |
| Popis: | Contains fulltext : 135934.pdf (Publisher’s version ) (Open Access) In order to develop affinity-based biosensor platforms, appropriate ligands with a functional handle for immobilization onto a biosensor surface are required. To this end, a library of papain inhibitors was designed and synthesized, containing different azide linkers for subsequent immobilization by 'click' chemistry, in this particular case by copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC). Furthermore, a molecular docking study was performed to obtain a better insight as to at which position such azide handles could be tolerated without affecting binding affinity. Although the azide moiety is small, in some cases its introduction strongly influenced the binding affinity. For one class of inhibitors a swapped binding mode was proposed to explain the results. In addition, a specific site for linker introduction was identified, which did not significantly affect the binding affinity. |
| Databáze: | OpenAIRE |
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