Fig. 4: Modeled complexes of AG10-L1-Nal and AG10-L2-Nal to both TTR and mu-opioid receptors. | Nature Communications

Fig. 4: Modeled complexes of AG10-L1-Nal and AG10-L2-Nal to both TTR and mu-opioid receptors.

From: Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects

Fig. 4

a The linker length for AG10-L1-Nal (~20 Å) is long enough to allow AG10-L1-Nal to bind to both the mu-opioid receptor and transthyretin (TTR) simultaneously. The AG10-L2-Nal linker is shorter which allows AG10-L2-Nal to bind to either b the mu-opioid receptor (pdb id: 4DKL)55 or c TTR (pdb id: 4HIQ)6 but not both proteins at the same time. Because of the higher affinity of AG10-L2-Nal to the mu-opioid receptor (Ki = 1.3 nM) over TTR (Kd = 333 nM), AG10-L2-Nal will preferentially bind to the mu-opioid receptor over TTR.

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