Antibodies currently represent more than half of the total sales of all biopharmaceutical products and their market size has been growing steadily. Because nature uses antibodies to fight against diseases, they have many advantages for therapeutic and diagnostic uses such as being highly target-specific, low immunogenicity, longer half-life and faster clinical approval. Most of therapeutic antibodies are full-length, but smaller antibody fragments are gaining more attention over the last decade. Right now, antibody fragments represent 10% of approved antibody therapeutics on the market but this number is increasing exponentially. Kalyoncu Lab aims to design, discover, engineer and characterize antibody fragments for therapeutic and diagnostic applications.
Our goal is to develop antibody fragments in several formats for therapeutic and diagnostic applications. Currently, our research interests are: (1) Development of antibody fragments such as Fab, scFv, VH from full-length antibodies and their test and characterization for therapeutic or diagnostic use. (2) Several protein engineering approaches such as linker design, protein fusions and conjugates to develop next-generation antibody fragments (3) Antibody discovery for novel targets by phage display and yeast surface display
Arslan M, Karadag D, Kalyoncu S. Conformational changes in a Vernier zone region: Implications for antibody dual specificity.. Proteins. 2020 November ; 88 (11) : 1447-1457. doi:10.1002/prot.25964.
Karadag M, Arslan M, Kaleli NE, Kalyoncu S. Physicochemical determinants of antibody-protein interactions.. Advances in protein chemistry and structural biology. 2020 January ; 121 : 85-114. doi:10.1016/bs.apcsb.2019.08.011.
Lou W, Stimple SD, Desai AA, Makowski EK, Kalyoncu S, Mogensen JE, Spang LT, Asgreen DJ, Staby A, Duus K, Amstrup J, Zhang Y, Tessier PM. Directed evolution of conformation-specific antibodies for sensitive detection of polypeptide aggregates in therapeutic drug formulations.. Biotechnology and bioengineering. 2020 October ; 118 (2) : 797-808. doi:10.1002/bit.27610.
Nazlı Eda Kaleli, Murat Karadag, Sibel Kalyoncu. Phage display derived therapeutic antibodies have enriched aliphatic content: Insights for developability issues. Proteins: Structure, Function, and Bioinformatics. 2019 July ; 87 (7) : 607-618. doi:10.1002/prot.25685.
Merve Arslan, Dilara Karadag, Sibel Kalyoncu. Protein engineering approaches for antibody fragments: directed evolution and rational design approaches. Turkish Journal of Biology. 2019 February ; 43 (1) : 1-12. doi:10.3906/biy-1809-28.
Stimple SD, Kalyoncu S, Desai AA, Mogensen JE, Spang LT, Asgreen DJ, Staby A, Tessier PM. Sensitive detection of glucagon aggregation using amyloid fibril‐specific antibodies. Biotechnology and Bioengineering. 2019 April . doi:10.1002/bit.26994.
Naing SH, Kalyoncu S, Smalley DM, Kim H, Tao X, George JB, Jonke AP, Oliver RC, Urban VS, Torres MP, Lieberman RL. Both positional and chemical variables control in vitro proteolytic cleavage of a presenilin ortholog. Journal of Biological Chemistry. 2018 March ; 293 (13) : 4653-4663. doi:10.1074/jbc.RA117.001436.
Kalyoncu S, Heaner DP Jr, Kurt Z, Bethel CM, Ukachukwu CU, Chakravarthy S, Spain JC, Lieberman RL. Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution.. Nature chemical biology. 2016 December ; 12 (12) : 1031-1036. doi:10.1038/nchembio.2191.
Johnson JL, Entzminger KC, Hyun J, Kalyoncu S, Heaner DP Jr, Morales IA, Sheppard A, Gumbart JC, Maynard JA, Lieberman RL. Structural and biophysical characterization of an epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization.. Acta crystallographica. Section D, Biological crystallography. 2015 April ; 71 (Pt 4) : 896-906. doi:10.1107/S1399004715001856.
Naing SH, Vukoti KM, Drury JE, Johnson JL, Kalyoncu S, Hill SE, Torres MP, Lieberman RL. Catalytic Properties of Intramembrane Aspartyl Protease Substrate Hydrolysis Evaluated Using a FRET Peptide Cleavage Assay.. ACS chemical biology. 2015 September ; 10 (9) : 2166-74. doi:10.1021/acschembio.5b00305.
Kalyoncu S, Hyun J, Pai JC, Johnson JL, Entzminger K, Jain A, Heaner DP Jr, Morales IA, Truskett TM, Maynard JA, Lieberman RL. Effects of protein engineering and rational mutagenesis on crystal lattice of single chain antibody fragments.. Proteins. 2014 September ; 82 (9) : 1884-95. doi:10.1002/prot.24542.
Kalyoncu S, Keskin O, Gursoy A. Interaction prediction and classification of PDZ domains.. BMC bioinformatics. 2010 June ; 11 : 357. doi:10.1186/1471-2105-11-357.
Total : 12
Physicochemical determinants of antibody-protein interactions (2020). APCSB: Protein Interactions as Targets in Drug Discovery. Elsevier.
Lessons from an α-Helical Membrane Enzyme: Expression, Purification, and Detergent Optimization for Biophysical and Structural Characterization (2016). Heterologous Expression of Membrane Proteins. Humana Press.
Total : 2
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Development of A Topical Therapy Approach for Macular Corneal Dystrophy, Ongoing
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Development and Prodcution of Lung Cancer Monoclonal Antibodies Commonly Used in Clinical Pathology, Ongoing
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Development of next-generation recombinant antibody fragments against VEGF for cancer therapy., Ongoing
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Makuler Kornea Distrofisinin In Vivo Modellemesi: Zebrabalığı Mutantlarının Crispr/Cas9 Ile Oluşturulması, Chst6?Nın Gelişimdeki Rolünün Ve Mkd Hastalık Fenotipinin Araştırılması, Ongoing
Other Private Sector - RD : Scientific and technological cooperation project for the development of new biopharmaceutical products to be used in the field of ophthalmology, Ongoing
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Development of Recombinant Protein Based Vaccine Against SARS-CoV-2, Ongoing
The Scientific and Technological Research Council of Turkey - TUBITAK - RD : Development of Drugs Based on “Ghost Receptor-Antibody” Against SARS-CoV-2, Ongoing