Fig. 1: Transport vehicles engineered at an Fc β-sheet surface bind with a range of affinities to CD98hc. | Nature Communications

Fig. 1: Transport vehicles engineered at an Fc β-sheet surface bind with a range of affinities to CD98hc.

From: CD98hc is a target for brain delivery of biotherapeutics

Fig. 1

a Cartoon of the ATVCD98hc bound to the CD98hc-LAT1 complex with the relative position of the membrane highlighted (dotted line). b Outline of the steps used to identify and engineer TVs. Positions in the naïve and maturation libraries are modeled onto the human IgG1 Fc ___domain (PDB ID: 1HZH) with positions randomized in the original library (orange), randomized expanded positions (green), unaltered original positions (tan), and unaltered peripheral positions (gray) highlighted. An example of one of ten patch libraries is provided. c Representative TV sequences from each stage are shown with corresponding affinities to human and cynomolgus CD98hc of the ATVCD98hc:DNP clone, as measured by surface-plasmon resonance. d A compilation of affinities of ATVCD98hc:DNP variants to human and cynomolgus CD98hc across rounds of maturation. e Immunocytochemistry detection of huIgG 1 h after incubation of ATVCD98hc:DNP (62.5 nM), anti-CD98hc (62.5 nM) and anti-DNP (500 nM) to human (HeLa), cynomolgus CD98hc-expressing cells (CHO: cynomolgus CD98hc) and parental cells (CHO). Representative images are shown from at least 15 images per well, n = 2 independent experiments. Scale bars = 50 µm. Source data are provided as a Source Data file.

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