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Molecular Imprinting Technology. Design and Recognition Properties of Antibody/Receptor Mimics

Författare:
  • Olof Ramström
Publiceringsår: 1996
Språk: Engelska
Sidor:
Dokumenttyp: Doktorsavhandling
Förlag: Pure and Applied Biochemistry, Lund University

Sammanfattning

Molecular imprinting technology is derived from the concept of creating designed recognition sites in macromolecular matrices by means of template polymerisation. Molecularly imprinted polymers are able to mimic recognition in natural binding events, such as antibody-antigen and receptor-ligand interactions. This thesis addresses some aspects of the preparation of molecularly imprinted polymers and focuses upon specific recognition perspectives. A brief introduction to the basis of molecular recognition is given.



The design of molecularly imprinted polymers following a self-assembly approach, using only non-covalent interactions between the imprint species and the functional monomers, is described. In addition to the use of methacrylic acid-based systems, special emphasis has been put on the use of combinations of functionally interacting monomers in order to acquire concerted actions of different functionalities in the resulting recognition matrices. Thus, the simultaneous action of two basically different monomers in the imprinting protocol resulted in improved recognition. Further, the use of derivatised silica beads as carriers for the polymers has been investigated.



The recognition properties of the prepared polymers have been focused upon. The polymers have been subjected to chromatographic analyses and equilibrium analyses, respectively, for the estimation of the specificities. The chiral recognition properties of the polymers have been used extensively as a diagnostic tool, and the recognition performances have been evaluated from the resulting enantioseparations. Furthermore, equilibrium binding analysis has been employed for the evaluation of the recognition by antibody mimics. The recognition ability in aqueous media has also been assessed. It has been demonstrated that the disrupting power of water on weak non-covalent interactions may be overcome in certain systems.



The prepared macromolecular matrices have been utilised in several applications. Primarily, the polymers have been used as chiral stationary phases for chromatographic separations and the recognition properties have been evaluated from the capability of selectively separating racemic mixtures. Special attention has been put on the chiral recognition of compounds comprising two chiral centres and it is demonstrated that the polymers can selectively distinguish the imprint molecule from the other stereoisomeric species. Another application is the use of a molecularly imprinted polymer as recognition element in a biosensor-like device. Fibre-optic measurements could be used to follow the recognition of a fluorescently-labelled compound by the polymer. A third application area is the use of molecularly imprinted polymers in immunoassay-like analyses. Polymers selective for steroid hormones were evaluated for their recognition specificities utilising standard immunoassay protocols. The resulting cross-reactivities of these artificial antibodies were similar to those obtained for natural antibodies.

Disputation

1996-05-21
10:15
Lecture Hall C, Chemical Center, Lund University
  • Meir Wilchek (Prof.)

Nyckelord

  • Biochemistry and Molecular Biology
  • Template Polymerisatio
  • Steroid
  • Receptor
  • Racemic Resolution
  • Polymer
  • Molecular Recognition
  • Molecular Imprinting
  • Enantiomeric Separation
  • de novo Design
  • Chromatography
  • Chiral Stationary Phase
  • Chiral Recognition
  • Biorecognition
  • Antibody
  • Biomimetic
  • Biochemistry
  • Metabolism
  • Biokemi
  • metabolism
  • Biotechnology
  • Bioteknik

Övriga

Published
  • ISBN: 91-628-2060-5
  • LUTKDH/TKBK-1039/1-222/1996

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