Development and differentiation of hyperstable consensus monobodies based on the type 3 fibronectin domain
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| Název: | Development and differentiation of hyperstable consensus monobodies based on the type 3 fibronectin domain |
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| Autoři: | PETER GEOFFREY CHANDLER |
| Rok vydání: | 2021 |
| Sbírka: | Monash University: Figshare |
| Témata: | Structural biology (incl. macromolecular modelling), Biochemistry and cell biology not elsewhere classified, Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies), Medical biochemistry - proteins and peptides (incl. medical proteomics), consensus design, stability–function trade-off, loop grafting, mini proteins, monobodies, adnectin, non-antibody scaffold, fibronectin, Biochemistry, Structural Biology, Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) |
| Popis: | Monobodies based on the type 3 fibronectin (FN3) domain are designed to overcome limitations of the antibody binding scaffold, being more simple and more amenable to the rigours of drug development. This thesis focuses on the development of FN3Con, a hyperstable consensus FN3 monobody. Through grafting of binding loops from monobodies of median stability, this work produced two FN3Con constructs with affinity to clinical targets and a shelf life of over 2 years at room temperature. The thesis then investigates methods to meaningfully differentiate monobodies from the antibody scaffold through buffer excipients, chemical conjugation and integration of native fibronectin characteristics. |
| Druh dokumentu: | thesis |
| Jazyk: | unknown |
| Relation: | https://figshare.com/articles/thesis/Development_and_differentiation_of_hyperstable_consensus_monobodies_based_on_the_type_3_fibronectin_domain/15051897 |
| DOI: | 10.26180/15051897.v1 |
| Dostupnost: | https://doi.org/10.26180/15051897.v1 https://figshare.com/articles/thesis/Development_and_differentiation_of_hyperstable_consensus_monobodies_based_on_the_type_3_fibronectin_domain/15051897 |
| Rights: | In Copyright |
| Přístupové číslo: | edsbas.B2500FFE |
| Databáze: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | Monobodies based on the type 3 fibronectin (FN3) domain are designed to overcome limitations of the antibody binding scaffold, being more simple and more amenable to the rigours of drug development. This thesis focuses on the development of FN3Con, a hyperstable consensus FN3 monobody. Through grafting of binding loops from monobodies of median stability, this work produced two FN3Con constructs with affinity to clinical targets and a shelf life of over 2 years at room temperature. The thesis then investigates methods to meaningfully differentiate monobodies from the antibody scaffold through buffer excipients, chemical conjugation and integration of native fibronectin characteristics. |
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| DOI: | 10.26180/15051897.v1 |