8dy2

Crystal Structure of spFv GLK1

spinqualitylabelsall models 8dy2, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dy2 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Single-chain fragment variable (scFv) domains play an important role in antibody-based therapeutic modalities, such as bispecifics, multispecifics and chimeric antigen receptor T cells or natural killer cells. However, scFv domains exhibit lower stability and increased risk of aggregation due to transient dissociation ("breathing") and inter-molecular reassociation of the two domains (VL and VH). We designed a novel strategy, referred to as stapling, that introduces two disulfide bonds between the scFv linker and the two variable domains to minimize scFv breathing. We named the resulting molecules stapled scFv (spFv). Stapling increased thermal stability (Tm) by an average of 10 degrees C. In multiple scFv/spFv multispecifics, the spFv molecules display significantly improved stability, minimal aggregation and superior product quality. These spFv multispecifics retain binding affinity and functionality. Our stapling design was compatible with all antibody variable regions we evaluated and may be widely applicable to stabilize scFv molecules for designing biotherapeutics with superior biophysical properties. "Stapling" scFv for multispecific biotherapeutics of superior properties.,Boucher LE, Prinslow EG, Feldkamp M, Yi F, Nanjunda R, Wu SJ, Liu T, Lacy ER, Jacobs S, Kozlyuk N, Del Rosario B, Wu B, Aquino P, Davidson RC, Heyne S, Mazzanti N, Testa J, Diem MD, Gorre E, Mahan A, Nanda H, Gunawardena HP, Gervais A, Armstrong AA, Teplyakov A, Huang C, Zwolak A, Chowdhury P, Cheung WC, Luo J MAbs. 2023 Jan-Dec;15(1):2195517. doi: 10.1080/19420862.2023.2195517. PMID:37074212 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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