We have highlighted one of our previous posts we optimized the yield in protein production by 330% compared to published literature: https://lnkd.in/dmrgTqpp
VCB serves as a critical component in PROTAC design by recruiting the target proteins via VHL. Formation of a ternary complex involving the target protein is required for targeted protein degradation (TPD). There is a need for novel chemical matter for VHL recruitment. Enhanced molecular characteristics of next-generation VHL binders could broaden the efficacy of VCB-mediated TPD.
After crystallizing the protein, a SmartSoak system was set up. We observed that SmartSoak improves the diffraction of the crystal by 0.5 Å. We SmartSoak’ed an in-house fragment library and identified novel binders. Four binders at EloC, one binder at the EloC-EloB (cryptic pocket) and three binders at VHL (cryptic and orthosteric).
Interestingly, two fragments bind at the cryptic pocket of VHL, inducing a more pronounced opening of the pocket compared to the published structures. The two fragments are well-positioned for linking.
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