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. 2021 Jan 21;28(1):70–77.e5. doi: 10.1016/j.chembiol.2020.11.002

Figure 2.

Figure 2

Screen of Panels of Chemical Mutants at the Three Most Accessible Positions in the CDR3 Loop with Non-canonical Side Chains

(A) List of the three chemical mutants tested at each of the three positions (E137, T138, and L139) in the CDR3 loop previously selected for their accessibility (Figure 1). We confirmed the chemical modifications by LC-MS, validated their structural integrity after the chemical mutagenesis by circular dichroism (CD), and assessed their potency in inhibiting Aβ aggregation by ThT fluorescence assays at three stoichiometries (1:2, 1:4, and 1:8). The installation of cysteamine at position T138 was selected for further studies.

(B and C) Comparison of the aggregation profiles of DesAb-Aβ(3–9) and DesAb-Aβ(3–9) (T138cysteamine); continuous lines represent the fit of the data using the integrated rate law for Aβ aggregation. The scatterplot represents the apparent decoupled primary and secondary nucleation rate constants for each dilution of the antibody.