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The Structure of Benzenesulfonamide-Terminated Thiol on Gold Surfaces and the Interaction with Carbonic Anhydrase
Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology, Computational Physics . Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Computational Physics . Linköping University, The Institute of Technology.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

A well-structured and robust biomolecular monolayer based upon a benzenesulfonamideterminated alkane thiol, to be used as a model system for molecular recognition processes, was prepared. The benzenesulfonamide-terminated thiol adsorbed onto gold substrates was characterized using X-ray photoelectron spectroscopy, near edge X-ray absorption fine structure spectroscopy, infrared-reflection absorption spectroscopy and ellipsometry. The results showed that the benzenesulfonamide-terminated alkane thiol forms a wellorganized molecular layer on the gold substrates. The orientation of the aromatic ring relative to the gold surface was investigated by means of the angle defined as the normal to the aromatic ring relative to the normal to the gold surface. It was shown that the average tilt angle is approximately 62º. In a second step, the  benzenesulfonamideterminated thiol monolayer was exposed to carbonic anhydrase, which is an enzyme and a therapeutic target. Benzenesulfonamides are used in biomedical applications as inhibitors for carbonic anhydrase. Our purpose in this study was to investigate the recognition capability of the benzenesulfonamide when designed as a thiol monolayer. The interaction between the benzenesulfonamide-terminated monolayer and carbonic anhydrase was studied using ellipsometry and surface plasmon resonance. The results show that the benzenesulfonamide-terminated thiol adsorbed onto the gold substrates is able to bind carbonic anhydrase. The results also indicate that the interaction is specific.

National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71456OAI: oai:DiVA.org:liu-71456DiVA: diva2:449088
Available from: 2011-10-19 Created: 2011-10-19 Last updated: 2011-10-19Bibliographically approved
In thesis
1. Structure analysis and molecular recognition studies of bio-functionalized surfaces
Open this publication in new window or tab >>Structure analysis and molecular recognition studies of bio-functionalized surfaces
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological and chemical reactions involved in physiological processes are often complex and very sophisticated. Such processes can be mimicked in the laboratory to obtain important knowledge, valuable for the  development of new diagnostic methods, drugs and biosensors. This  thesis includes investigations of bio-functionalized surfaces that can be used as model systems to mimic naturally existing biomolecular recognition processes.

In this thesis, three different peptides, of our own design, that mimic parts of the second and third intracellular loops of the α2A-adrenergic receptor, are studied. The peptides were immobilized onto gold substrates, through thiol chemistry. The interaction between the peptides and the G-protein was investigated using surface plasmon resonance (SPR). The G-protein showed the highest binding capability for surfaces functionalized with a peptide mimicking the n-terminal of the third intracellular loop (GPR-i3n). The binding was enhanced when the pure GPR-i3n peptide was mixed with a short oligopeptide (3GC). A tentative explanation for the obtained results is that the presence of the 3GC molecule enables conformational changes of the GPR-i3n monolayer which affect the interaction with the G-protein. The results from the SPR measurements also indicated that the conformation of the G-protein was kept intact during the interaction with a peptide mimicking the c-terminal of the third intracellular loop (GPR-i3c). Multilayers were formed on the surfaces functionalized with a peptide mimicking the second intracellular loop (GPR-i2c) and the GPR-i3n peptide. We suggest that conformational changes of the G-protein are induced during the interaction with the surfaces functionalized with the GPR-i3n and GPR-i2c peptides.

Comprehensive surface characterizations of four biomolecular systems, based upon the functional groups: noradrenaline, phenylboronic-ester, phenylboronic-acid and benzenesulfonamide, are presented in the thesis. The aim is to develop a platform for detailed molecular recognition studies on surfaces. The molecular systems were characterized using infrared spectroscopy, X-ray photoelectron spectroscopy, near edge X-ray absorption fine structure spectroscopy, ellipsometry and contact angle goniometry. Noradrenaline was chosen as it is a neurotransmitter that interacts with the extracellular loops of adrenergic receptors. In this work, the noradrenaline analogue (Nor-Pt) of our own design, was equipped with a -SH handle to be linked to surfaces and with the free noradrenaline group available for interaction studies. The Nor-Pt molecules were organized on the surfaces with the sulfur atom close to the gold substrate and the aromatic ring available for possible interactions with other biomolecules in the ambient media. The main component of the C=O vibrational mode present in the amide moiety had a parallel orientation relative to the plane of the gold surface, based on the infrared spectroscopy results. The phenylboronic system was designed as a simple mimicry of an  adrenergic receptor as the boronic acid functional group binds to diol containing molecules such as noradrenaline. The boronic  esterterminated alkane thiol (BOR-Capped) was chemisorbed onto gold substrates. We showed that BOR-Capped was linked to the gold substrate via thiolate bond formation and formed a well-organized monolayer. The pinacolyl protection group was removed directly from the BOR-Capped monolayer on the surfaces, which resulted in an unprotected monolayer terminated with the boronic acid functional group (BOR-Uncapped). The strong chemical bond to the gold substrate was retained during the deprotection procedure as only thiolate sulfur species were observed for the BOR-Uncapped molecular system. The benzenesulfonamide based molecule was designed as a model system for bioselective surfaces. An amine-terminated alkane thiol was adsorbed onto a gold substrate. In a second step, a benzenesulfonamide derivative was linked to the amine-terminated monolayer by the formation of an amide bond. We showed that the resulting benzenesulfonamide-terminated alkane thiol (AUT-C6) formed a well-organized and semi-thick monolayer on the gold substrate. The polarization dependence of NEXAFS was used to determine the average tilt angle of the aromatic ring structures of Nor-Pt, BOR-Capped, BOR-Uncapped and AUT-C6. The results indicate that the aromatic ring planes of BOR-Capped and AUT-C6 have a preferential orientation toward the surface normal. The aromatic ring structures of Nor-Pt and BOR-Uncapped were determined to have a more tilted orientation relative to the gold surface normal.

Finally, the interaction between carbonic anhydrase and the AUT-C6 molecule was investigated using surface plasmon resonance and ellipsometry. The surface immobilized benzenesulfonamide was shown to bind to carbonic anhydrase and the results indicated that the interaction is specific.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 56 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1404
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-71457 (URN)978–91–7393–050–5 (ISBN)
Public defence
2011-11-11, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (Swedish)
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Supervisors
Available from: 2011-10-19 Created: 2011-10-19 Last updated: 2015-06-03Bibliographically approved

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Vahlberg, CeciliaSkoglund, CarolineLinares, MathieuNorman, PatrickUvdal, Jahsa

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