Structure of Nanobody Nb23

Background: Nanobodies, or VHHs, are derived from heavy chain-only antibodies (hcAbs) found in camelids. They overcome some of the inherent limitations monoclonal (mAbs) and derivatives thereof, due to their smaller molecular size higher stability, thus present an alternative mAbs for therapeutic use. Two nanobodies, Nb23 Nb24, have been shown similarly inhibit self-aggregation very amyloidogenic variants ?2-microglobulin. Here, structure was modeled with Chemical-Shift (CS)-Rosetta server using chemical shift assignments nuclear magnetic resonance (NMR) spectroscopy experiments, used as prior knowledge PONDEROSA restrained modeling based on experimentally assessed internuclear distances. Further validation comparatively obtained results dynamics trajectories calculated resulting best energy-minimized conformers. Methods: 2D 3D NMR experiments were carried out determine assignment backbone side chain hydrogen, nitrogen carbon resonances extract shifts interproton separations modeling. Results: The solution isolated nanobody determined. Conclusions: structural analysis indicated that has a dynamic CDR3 loop distributed over different orientations respect which could differences target antigen affinity complex lability.