6TWC
Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Double Bridged Peptide F21
Summary for 6TWC
| Entry DOI | 10.2210/pdb6twc/pdb |
| Descriptor | Coagulation factor XI, Double Bridged Peptide F21, ACETONE, ... (4 entities in total) |
| Functional Keywords | protease, coagulation factors, inhibitor, double bridged peptide, phage display, blood clotting |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 31304.73 |
| Authors | Kong, X.D.,Pojer, F.,Heinis, C. (deposition date: 2020-01-13, release date: 2020-05-20, Last modification date: 2024-01-24) |
| Primary citation | Kong, X.D.,Moriya, J.,Carle, V.,Pojer, F.,Abriata, L.A.,Deyle, K.,Heinis, C. De novo development of proteolytically resistant therapeutic peptides for oral administration. Nat Biomed Eng, 4:560-571, 2020 Cited by PubMed Abstract: The oral administration of peptide drugs is hampered by their metabolic instability and limited intestinal uptake. Here, we describe a method for the generation of small target-specific peptides (less than 1,600 Da in size) that resist gastrointestinal proteases. By using phage display to screen large libraries of genetically encoded double-bridged peptides on protease-resistant fd bacteriophages, we generated a peptide inhibitor of the coagulation Factor XIa with nanomolar affinity that resisted gastrointestinal proteases in all regions of the gastrointestinal tract of mice after oral administration, enabling more than 30% of the peptide to remain intact, and small quantities of it to reach the blood circulation. We also developed a gastrointestinal-protease-resistant peptide antagonist for the interleukin-23 receptor, which has a role in the pathogenesis of Crohn's disease and ulcerative colitis. The de novo generation of targeted peptides that resist proteolytic degradation in the gastrointestinal tract should help the development of effective peptides for oral delivery. PubMed: 32393891DOI: 10.1038/s41551-020-0556-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.86 Å) |
Structure validation
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