AI Article Synopsis
- Spatial organization and conformational changes of antibodies significantly influence their biological functions.
- The study evaluated the impact of V H domain arrangement in bispecific antibodies on TNF retention and inhibition in relation to murine myeloid cells.
- Key findings highlighted that the 'superflexible' linker was essential for the activity of certain antibodies, while the orientation of modules was less critical for those with a 'semi-rigid' linker, suggesting pathways for improving drug design.
Article Abstract
Spatial organization and conformational changes of antibodies may significantly affect their biological functions. We assessed the effect of mutual organization of the two V H domains within bispecific antibodies recognizing human TNF and the surface molecules of murine myeloid cells (F4/80 or CD11b) on TNF retention and inhibition. TNF-neutralizing properties in vitro and in vivo of MYSTI-2 and MYSTI-3 antibodies were compared with new variants with interchanged V H domains and different linker sequences. The most effective structure of MYSTI-2 and MYSTI-3 proteins required the Ser/Gly-containing 'superflexible' linker. The orientation of the modules was crucial for the activity of the proteins, but not for MYSTI-3 with the Pro/Gln-containing 'semi-rigid' linker. Our results may contribute toward the development of more effective drug prototypes.
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| http://dx.doi.org/10.1002/1873-3468.13913 | DOI Listing |
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