Jindrich (Henry) Kopecek
Distinguished Professor of Pharmaceutics & Pharmaceutical Chemistry and Distinguished Professor of Bioengineering
M.S. Institute of Chemical Technology, Czechoslovakia
Ph.D. Institute of Macromolecular Chemistry, Czechoslovakia
D.Sc. Czechoslovak Academy of Sciences, Czechoslovakia
Research
Research in the Kopecek Research Group (link above) focuses on the design, synthesis and characterization of biorecognizable biomedical polymers.
Targetable polymeric anticancer drugs. Targetable water-soluble polymeric carriers are studied which contain recognition moieties, such as antibodies (or their fragments), saccharides, or oligopeptide epitopes, which presence leads to interaction with cell-surface antigens or receptors and specific uptake into the target (cancer) cells. Two ways of drug activation in the target tissue are evaluated: release of the drug (anthracycline and benzoquinone ansamycin antibiotics) by lysosomal cysteine proteinases and activation by light (photosensitizers, e.g. chlorin e6). The fate of polymer-drug conjugates on cellular and subcellular levels, as well as factors influencing biorecognition, such as chemical structure, aggregation and association of macromolecules in solution are being systematically studied. The potential of polymeric anticancer drugs to overcome multidrug resistance and the cell signaling pathways involved in modified gene expression (when compared to low molecular weight drugs) are the focus of current studies. Several polymeric anticancer drug conjugates are being evaluated in clinical trials.
Novel approaches for the treatment of osteoporosis. Targeted drug delivery systems are being evaluated containing moieties to vector the conjugates toward hard tissue. Attachment of anabolic agents to the conjugates via spacers containing cathepsin K sensitive oligopeptide sequences will result in site-specific release, recruitment of osteoblasts, and bone formation.
Genetically engineered biomaterials. The use of the coiled-coil motif in the design and synthesis of new genetically engineered biomaterials and drug delivery systems is being studied. The goal of the project is to design graft and block copolymers, whose reversible assembly into smart hydrogels will be modulated by the association of coiled-coil peptide domains.
References
1. Kopecek J, Yang J (2007) Hydrogels as Smart Biomaterials. Polymer Int. DOI:10.1002/pi.2253
2. Gao S, Lu ZR, Kopeckova P, Kopecek J (2007) Biodistribution and Pharmacokinetics of Colon-Specific HPMA Copolymer – 9-Aminocamptothecin Conjugate in Mice. J. Controlled Release 117:179-185
3. Ding H, Prodinger W, Kopecek J (2007) Two-Step Fluorescence Screening of CD21-Binding Peptides with One-Bead One-Compound Library and Investigation of Binding Properties of HPMA Copolymer-Peptide Conjugates. Biomacromolecules 7:3037-3046
4. Yang J, Xu C, Wang C, Kopecek J (2006) Refolding Hydrogels Self-Assembled from HPMA Graft Copolymers by Antiparallel Coiled-Coil Formation. Biomacromolecules 7:1187-1195
5. Wang D, Sima M, Mosley RL, Davda JP, Tietze N, Miller SC, Gwilt PR, Kopeckova P, Kopecek J (2006) Pharmacokinetic and Biodistribution Studies of a Bone-targeting Drug Delivery System Based on N-(2-Hydroxypropyl)methacrylamide (HPMA) Copolymers. Molecular Pharmaceutics 3:717-725
6. Malugin A, Kopeckova P, Kopecek J (2006) HPMA Copolymer-Bound Doxorubicin Induces Apoptosis in Ovarian Carcinoma Cells by the Disruption of Mitochondrial Function. Molecular Pharmaceutics 3:351-361
7. Xu C, Breedveld V, Kopecek J (2005) Reversible Hydrogels from Self-Assembling Genetically Engineered Protein Block Copolymers. Biomacromolecules 6:1739-1749
8. Nori A, Kopecek J (2005) Intracellular Targeting of Polymer-Bound Drugs for Cancer Chemotherapy. Adv. Drug Delivery Rev. 57:609-636
9. Nishiyama N, Nori A, Malugin A, Kasuya Y, Kopeckova P, Kopecek J (2003) Free and N-(2-Hydroxypropyl)methacrylamide (HPMA) Copolymer-bound Geldanamycin Derivative Induce Different Stress Responses in A2780 Human Ovarian Carcinoma Cells. Cancer Res. 63:7876-7882
10. Kopecek J (2003) Smart and Genetically Engineered Biomaterials and Drug Delivery Systems. Eur. J. Pharm. Sci. 20:1-16
11. Merdan T, Callahan J, Petersen H, Kunath K, Bakowsky U, Kopeckova P, Kissel T, Kopecek J (2003) Pegylated Polyethylenimine – Fab’ Antibody Fragment Conjugates for Targeted Gene Delivery to Human Ovarian Carcinoma Cells. Bioconjugate Chem. 14:989-996
12. Wang C, Stewart RJ, Kopecek J (1999) Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature 397:417-420
13. Lu ZR, Kopeckova P, Kopecek J (1999) Polymerizable Fab’ Antibody Fragments for Targeting of Anticancer Drugs. Nature Biotechnology 17:1101-1104
