It’s really meaningful to have such insightful coverage from a leader in the field @zenbrainest.bsky.social and Xianglin Huang. We appreciate the time they took to write up this very nice commentary!

Thanks Anirban! Glad to see this work released

#chembio 🧪

ii. Recognition that these nanobody-ligand conjugated only show activity when both the nanobody AND ligand targets are expressed (logic gated signaling). This should be useful for delivering molecules with widely expressed targets only to cells of choice! Congrats to Shivani Sachdev and Swarnali Roy

This work described for the first time two new directions we are excited to explore: I. nanobody-small molecule conjugates as a sort of analogue of traditional antibody-drug conjugates but we are targeting GPCRs at the cell surface instead of intracellular targets.

Next up, a collaboration with Ross Cheloha's group (@rche54 <a href="https://bsky.app/profile/did:plc:ycxfqyv32syaeu347y4xquiw" class="hover:underline text-blue-600 dark:text-sky-400 no-card-link" target="_blank" rel="noopener" data-link="bsky-mention">@rche54.bsky.social) and @MitchellHo leveraging a novel self-labeling approach for site-specific modification of nanobodies for biological applications.

doi.org/10.1002/advs...
3/5

The findings suggest that optimizing input parameters and refining competition-based modeling approaches may enhance predictive accuracy for antibody-antigen interactions. Intriguing.

🧪 #chembio

Finally we compared models of nanobody-epitope to nanobody-antigen complexes. In one case Alphafold produced an accurate model with epitope but failed with antigen! This highlights the potential utility of simplifying Alphafold inputs for generating models with improved accuracies (4/4)

We further showed that Alphafold could be used in a competition mode to identify peptides that bound nanobody with higher affinity than the wild type epitope peptide. We also used modeling to guide design of a peptide-electrophile conjugate that forms a crosslink with nanobody (3/n)

We performed modeling of experimentally characterized nanobody-peptide interactions and found that 4/6 models matched experimental data. We also crystallized a new nanobody-peptide complex and showed good concordance between the x-ray structure (my first listing on the pdb!) (2/n)

We’re excited to apply this for cell-type specific targeting of gpcrs! Congrats to postdocs Shivani Sachdev and Swarnali Roy on the great work (3/3)