Selected research papers and reviews

a. Immobilization of biomolecules

The first reported immobilization of cells by entrapment in 1966 for use in the production of biochemicals.
Entrapment of Enzymes and Microorganisms in Synthetic Cross-Linked Polymers and Their Application in Column Techniques.
Acta Chem. Scand. 20, 2807-2810, 1966.
K. Mosbach and R. Mosbach

The application for industrial purposes of living immobilized microorganisms in 1970.
Preparation and Application of Polymer-Entrapped Enzymes and Microorganisms in Microbial Transformation Processes with Special Reference to Steroid 11-ß-Hydroxylation and 1-Dehydrogenation.
Biotechnol. Bioeng. XII, 19-27, 1970.
K. Mosbach and P.-O. Larsson.

The preparation and study of immobilized multi-enzyme systems in 1970.
Matrix-Bound Enzymes.
Part I. The Use of Different Acrylic Copolymers as Matrices.
Acta Chem. Scand. 24, 2084-2092, 1970.
K. Mosbach.

Matrix-Bound Enzymes.
Part II. Studies on a Matrix-Bound Two-Enzyme System.
Acta Chem. Scand. 24, 2093-2100, 1970
K. Mosbach and B. Mattiasson.
Entrapment of animal cells including insulin producing Langerhans islets, 1980.
Preparation of Immobilized Animals Cells.
FEBS Lett. 118, 145-150, 1980.
K. Nilsson and K. Mosbach.

Entrapment of animal cells for production of monoclonal antibodies, 1983.
Entrapment of Animal Cells for Production of Monoclonal Antibodies and Other Biomolecules.
Nature 302, 629-630, 1983.
K. Nilsson, W. Scheirer, O.W. Merten, L. Ostberg, E. Liehl, H.W.D. Katinger and K. Mosbach.

New immobilization method, sulfonyl halides (now commercially available) leading to stable linkages, 1981.
Immobilization of Enzymes and Affinity Ligands to Various Hydroxyl Group Carrying Supports Using Highly Reactive Sulfonyl Chlorides.
Biochem. Biophys. Res. Commun. 102, 449-457, 1981.
K. Nilsson and K. Mosbach

First immobilization of cells obtained by recombinant DNA-techniques (production of proinsulin) 1983.
Formation of Proinsulin by Immobilized Bacillus subtilis.
Nature 302, 543-545, 1983.
K. Mosbach, S. Birnbaum, K. Hardy, J. Davies and L. Bülow.

Development of microcarriers (gelatin beads) for animal cell culture, 1986.
Growth of Anchorage-Dependent Cells on Macroporuous Microcarriers.
Bio/Technology 4, 989-990, 1986.
K. Nilsson, F. Buzsaky and K. Mosbach.

b. Biosensor Technology

The development of biosensors, in particular the enzyme thermistor, 1974.
An Enzyme Thermistor.
Biochim. Biophys. Acta 364, 140-145, 1974.
K. Mosbach and B. Danielsson.

c. Miscellanous

Enzymic synthesis in organic solvents since 1983.
Continuous Synthesis of Amino Acid Ester Through Immobilized a-Chymotrypsin.
Annual Meeting of the Agricultural Chemical Society of Japan, 1983, p.480.
T. Mori, K. Nilsson, P.-O. Larsson and K. Mosbach.

Probably first gene fusion of enzymes acting in sequence to create artificial multienzyme systems, since 1985 (related to multienzyme studies, a)
Preparation of a Soluble Bifunctional Enzyme by Gene Fusion.
Bio/Technology 3, 821-823, 1985.
L. Bülow, P. Ljungcrantz and K. Mosbach.

Modification of enzyme specificity by "bio-imprinting", 1990 (related to molecular imprinting, II).
Induced Stereoselectivity and Substrate Selectivity of Bio-Imprinted a-Chymotrypsin in Anhydrous Organic Media.
J. Am. Chem. Soc. 113, 9366-9368, 1991.
M. Stahl, U. Jeppsson-Wistrand, M.-O. Mansson and K. Mosbach.

Horse Liver Alcohol Dehydrogenase Can Accept NADP+ as Coenzyme in High Concentrations of Acetonitrile.
Eur. J. Biochem. 227, 551-555 (1995).
A. Johansson, K. Mosbach and M.-O. Mansson.

d. Molecular recognition

I. Affinity techniques

The design of active immobilized coenzymes in 1971.
Preparation of a NAD(H)-Polymer Matrix Showing Coenzymic Function of the Bound Pyridine Nucleotide.
Biotechnol. Bioeng. XIII, 393-398, 1972.
P.-O. Larsson and K. Mosbach.

General ligand (group specific) affinity chromatography in 1971.
General Ligands and (Co)Substrate Elution in Affinity Chromatography.
Biochem. J. 127, 12-13, 1971.
K. Mosbach, H. Guilford, R. Ohlsson and M. Scott.

The construction of new artificial enzyme-coenzyme complexes in 1975.
Preparation of an Alcohol-Dehydrogenase - NAD(H) - Sepharose Complex Showing No Requirement of Soluble Coenzyme for Its Activity.
Eur. J. Biochem. 57, 529-535k, 1975.
S. Gestrelius, M.-O. Mansson and K. Mosbach.

Site-to-Site Directed Immobilization of Enzymes with bis-NAD Analogues.
Proc. Natl. Acad. Sci., USA, 80, 1487-1491 (1983).
M.-O. Mansson, N. Siegbahn and K. Mosbach.

Magnetic affinity chromatography.
Magnetic Ferrofluids for Preparation of Magnetic Polymers and Their Application in Affinity Chromatography.
Nature 270, 259-261 (1977).
K. Mosbach and L. Andersson.
Magnetic Polymer Particles.
US Patent 4,335,094. June 15, 1982.
K. Mosbach

High performance liquid affinity chromatography, 1978.
High Performance Liquid Affinity Chromatography (HPLAC) and Ist Application to the Separation Enzymes and Antigens.
FEBS Lett. 93, 5-9, 1978.
S. Ohlson, L. Hansson, P.-O. Larsson and K. Mosbach.

Affinity precipitation of enzymes, 1978.
Affinity Precipitation of Enzymes.
FEBS Lett. 98, 333-338, 1979.
P.-O. Larsson and K. Mosbach.

II. Molecular imprinting

Klaus Mosbach has created a "Center for molecular imprinting" at the University of Lund, Sweden. The number of original articles in the area of "molecular imprinting" he has published is dominant exceeding 150 plus 25 patents/applications (mainly based on non-covalent imprinting) together with his many students, post docs and guest professors. In one of his first papers, Synthesis of Substrate-Selective Polymers by Host-Guest Polymerization, Makromol. Chem. 182, 687-692 (1981), R. Arshady and K. Mosbach, K. Mosbach used the word "imprints" and for the first time described the principle of noncovalent imprinting, which was followed by an article on molecular imprinting by him the following year. His team thus became instrumental for the development of the area, as by now by far most published work uses the non-covalent approach - they also created in Lund "the Society of Molecular Imprinting". Below some selected papers describing different aspects are listed.

1. Separation

"Molecular imprinting" of molecules for development of separation material and artificial enzymes: Examples:
Synthesis of Substrate-Selective Polymers by Host-Guest Polymerization.
Makromol. Chem. 182, 687-692, 1981.
R. Arshady and K. Mosbach.

Highly Enantioselective and Substrate-Selective Polymers Obtained by Molecular Imprinting Utilizing Noncovalent Interactions. NMR and Chromatographic Studies on the Nature of Recognition.
J. Am. Chem. Soc. 110, 5853-5860, 1988.
B. Sellergren, M. Lepistö and K. Mosbach.

First preparation of synthetic antibody-binding mimics ("plastibodies").
Drug Assay Using Antibody Mimics Made by Molecular Imprinting.
Nature 361, 645-647 (1993).
G. Vlatakis, L.I. Andersson, R. Müller and K. Mosbach.

Preparation of artificial receptors.
Mimics of the Binding Sites of Opioid Receptors Obtained by Molecular Imprinting of Enkephalin and Morphine.
Proc. Natl. Acad. Sci. USA 92, 4788-4792 (1995).
L.I. Andersson, R. Müller, G. Vlatakis and K. Mosbach.

First successful imprinting of enzymes.
An Approach Towards Surface Imprinting Using the Enzyme Ribonuclease A.
J. Mol. Recognition 8, 35-39 (1995).
M. Kempe, M. Glad and K. Mosbach.

Preparation of Synthetic Enzymes and Synthetic Antibodies and Use of the Thus Prepared Enzymes and Antibodies.
US Patent 5,110,833. May 5, 1992.
K. Mosbach

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2. Enzyme mimics

First studies of enzyme mimics using molecular imprinting, 1987.
Enzyme-Mimicking Polymers Exhibiting Specific Substrate Binding and Catalytic Functions.
Reactive Polymers 6, 285-290, 1987.
A. Leonhardt and K. Mosbach.

Molecular Imprinting of a Transition State Analogue Leads to a Polymer Exhibiting Esterolytic Activity.
J. Chem. Soc, Chem. Commun, 14, 969-970 (1989).
D.K. Robinson and K. Mosbach.

(see also Ramström, O. and Mosbach, K. Synthesis and Catalyses by Molecularly Imprinted Materials. Curr. Op. Chem. Biol. 3, 759 (1999).

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3. Sensors

Studies with molecular imprints as substitute for biomolecules in sensors, 1993.
Some Studies of Molecularly-Imprinted Polymer Membranes in Combination with Field-Effect Devices.
Sensors and Actuators A, 37-38, 796-799, 1993.
E. Hedborg, F. Winquist, I. Lundström, L.I. Andersson and K. Mosbach.

Introducing Biomimetic Sensors Based on Molecularly Imprinted Polymers as Recognition Elements.
Anal. Chem. 67, 2142-2144, 1995.
D. Kriz, O. Ramström, A. Svensson and K. Mosbach.

4. Second generation of imprints

Mention should also be made to Klaus Mosbach's recent work towards what he calls the second or next generation in Molecular imprinting, encompassing both the anti-ideotypic approach and direct molding.

Toward the next generation of molecular imprinting with emphasis on the formation, by direct molding of compounds with biological activity (biomimetics)
Anal. Chem. Acta 435, 3-8, 2001.
K. Mosbach.

Generation of New Enzyme Inhibitors Using Imprinting Binding Sites: The Anti-Idiotypic Approach, a Step toward the Next Generation of Molecular Imprinting.
Journ. Of the American Chem. Soc. 123 (49), 12420-12421, 2001.
K. Mosbach, Y. Yu, J. Andersch and L. Ye.

Formation of a class of enzyme inhibitors , including a chiral compound, using imprinted polymers or biomolecules as molecular-scale reaction vessels.
Angew. Chem. Int. Ed., 41, 445, 2002.
Y. Yu, L. Ye, K. Haupt and K. Mosbach

Methods for Direct Synthesis of Compounds Having Complementary Structure to a Desired Molecular Entity and Use Thereof.
US Patent 6,127,154.
K. Mosbach, P.A.G. Cormack, O. Ramström and K. Haupt.

In the latter, an enzyme or antibody is used as "vessel" to prepare e.g. an inhibitor (drug) inside the cavity.
Both approaches could lead to new drugs or affinity ligands through this totally new approach (with the anti-ideotypic and direct approach a new inhibitor has already been obtained by the group).

June 16, 2004