8c7j: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8c7j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C7J FirstGlance]. <br> | <table><tr><td colspan='2'>[[8c7j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C7J FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8c7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c7j OCA], [https://pdbe.org/8c7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c7j RCSB], [https://www.ebi.ac.uk/pdbsum/8c7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c7j ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8c7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c7j OCA], [https://pdbe.org/8c7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c7j RCSB], [https://www.ebi.ac.uk/pdbsum/8c7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c7j ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 12:31, 17 October 2024
Phage display derived serum albumin binding knob domain engineered within a novel VH framework 3 bispecific antibody formatPhage display derived serum albumin binding knob domain engineered within a novel VH framework 3 bispecific antibody format
Structural highlights
Publication Abstract from PubMedBACKGROUND: Serum albumin binding is an established mechanism to extend the serum half-life of antibody fragments and peptides. The cysteine rich knob domains, isolated from bovine antibody ultralong CDRH3, are the smallest single chain antibody fragments described to date and versatile tools for protein engineering. METHODS: Here, we used phage display of bovine immune material to derive knob domains against human and rodent serum albumins. These were used to engineer bispecific Fab fragments, by using the framework III loop as a site for knob domain insertion. RESULTS: By this route, neutralisation of the canonical antigen (TNFalpha) was retained but extended pharmacokinetics in-vivo were achieved through albumin binding. Structural characterisation revealed correct folding of the knob domain and identified broadly common but non-cross-reactive epitopes. Additionally, we show that these albumin binding knob domains can be chemically synthesised to achieve dual IL-17A neutralisation and albumin binding in a single chemical entity. CONCLUSIONS: This study enables antibody and chemical engineering from bovine immune material, via an accessible discovery platform. Serum albumin binding knob domains engineered within a V(H) framework III bispecific antibody format and as chimeric peptides.,Adams R, Joyce C, Kuravskiy M, Harrison K, Ahdash Z, Balmforth M, Chia K, Marceddu C, Coates M, Snowden J, Goursaud E, Menochet K, van den Elsen J, Payne RJ, Lawson ADG, Scott-Tucker A, Macpherson A Front Immunol. 2023 May 12;14:1170357. doi: 10.3389/fimmu.2023.1170357. , eCollection 2023. PMID:37251411[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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