Anne Conibear, BSc MSc PhD

Anne Conibear, BSc MSc PhD

E-Mail: anne.conibear@univie.ac.at
Department of Biological Chemistry

Project: "SAbs" - Synthetic antibodies for cancer therapy

The goal of my interdisciplinary cancer research project is to use chemical synthesis techniques to make biological antibody-like molecules for use in cancer therapy. Antibodies are already used for cancer treatment and are one of the body’s natural strategies for fighting infections and removing damaged cells. They comprise two functional regions: an ‘antigen-binding’ region, which specifically recognizes proteins on foreign or defective cells, and an ‘effector’ region, which attracts the immune system to destroy them. The result is that foreign or defective cells are destroyed with minimal damage to normal tissue.

Chemical synthesis techniques can be used to make ‘binder’ and ‘effector’ peptides that have the same respective functions. Our novel approach is to join two or more of the ‘binder’ and ‘effector’ peptides together via a linker to make a ‘synthetic antibody’. Using chemical synthesis allows for precise control over the molecules and the flexibility to design and optimize how they bind to proteins on cancer cells. Furthermore, the strategy of linking various binders and effectors together gives us the versatility to make synthetic antibodies that bind to more than one cancer target protein, thereby increasing the specificity and ensuring that normal cells are not targeted. In my project, I aim to develop new chemical methods for linking binder and effector peptides so that we can understand more about how they work together and improve the specificity and activity of synthetic antibodies as novel cancer therapies.

Publications

  • Conibear, A. C., Farbiarz, K., Mayer, R.L., Matveenko, M., Kähligd, Becker, C. Arginine side-chain modification that occurs during copper-catalysed azide–alkyne click reactions resembles an advanced glycation end product. Org. Biomol. Chem., 2016,14, 6205-6211.

  • Kwon S, Bosmans F, Kaas Q, Cheneval O, Conibear AC, Rosengren KJ, Wang CK, Schroeder CI, Craik DJ. Efficient enzymatic cyclization of an inhibitory cystine knot-containing peptide. Biotechnol Bioeng. 2016 Oct;113(10):2202-12. doi: 10.1002/bit.25993. Epub 2016 Aug 9.

  • Wang CK, King GJ, Conibear AC, Ramos MC, Chaousis S, Henriques ST, Craik DJ. Mirror Images of Antimicrobial Peptides Provide Reflections on Their Functions and Amyloidogenic Properties. J Am Chem Soc. 2016 May 4;138(17):5706-13. doi: 10.1021/jacs.6b02575. Epub 2016 Apr 26.

  • Conibear AC, Chaousis S, Durek T, Rosengren KJ, Craik DJ, Schroeder CI. Approaches to the stabilization of bioactive epitopes by grafting and peptide cyclization. Biopolymers. 2016 Jan;106(1):89-100. doi: 10.1002/bip.22767.

  • Akcan M, Clark RJ, Daly NL, Conibear AC, de Faoite A, Heghinian MD, Sahil T, Adams DJ, Marí F, Craik DJ. Transforming conotoxins into cyclotides: Backbone cyclization of P-superfamily conotoxins. Biopolymers. 2015 Nov;104(6):682-92. doi: 10.1002/bip.22699.

  • Conibear, A. C., Wang, C. K., Bi, T., Rosengren, K. J., Camarero, J. A., and Craik, D. J. Insights into the molecular flexibility of theta-defensins by NMR relaxation analysis, J. Phys. Chem. B 2014, 118, 14257-14266.

  • Conibear, A. C. and Craik, D. J. The chemistry and biology of theta-defensins, Angew. Chem. Int. Ed. Engl. 2014, 53, 10612-10623.

  • Conibear, A. C., Bochen, A., Rosengren, K. J., Stupar, P., Wang, C., Kessler, H., and Craik, D. J. The cyclic cystine ladder of theta-defensins as a stable, bi-functional scaffold: A proof-of-concept study using the integrin-binding RGD motif, ChemBioChem 2014, 15, 451-459.

  • Conibear, A. C., Rosengren, K. J., Daly, N. L., Henriques, S. T., and Craik, D. J. The cyclic cystine ladder in theta-defensins is important for structure and stability, but not antibacterial activity, J. Biol. Chem. 2013, 288, 10830-10840.

  • Bodill, T., Conibear, A. C., Mutorwa, M. K., Goble, J. L., Blatch, G. L., Lobb, K. A., Klein, R., and Kaye, P. T. Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors, Bioorg. Med. Chem. 2013, 21, 4332-4341.

  • Conibear, A. C., Rosengren, K. J., Harvey, P. J., and Craik, D. J. Structural characterization of the cyclic cystine ladder motif of theta-defensins, Biochemistry 2012, 51, 9718-9726.

  • Conibear, A. C., Daly, N. L., and Craik, D. J. Quantification of small cyclic disulfide-rich peptides, Biopolymers 2012, 98, 518-524.

  • Conibear, A. C., and Craik, D. J. Chemical synthesis of naturally-occurring cyclic mini-proteins from plants and animals, Israel J. Chem. 2011, 51, 908-916.

  • Craik, D. J., and Conibear, A. C. The chemistry of cyclotides, J. Org. Chem. 2011, 76, 4805-4817.

  • Bodill, T., Conibear, A. C., Blatch, G. L., Lobb, K. A., and Kaye, P. T. Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors, Bioorg. Med. Chem. 2011, 19, 1321-1327.

  • Conibear, A. C., Lobb, K. A., and Kaye, P. T. 31P NMR kinetic study of the tandem cleavage of phosphonate esters by bromotrimethylsilane, Tetrahedron 2010, 66, 8446-8449.