Fig. 1 | Nature Communications

Fig. 1

From: Glutamic acid–valine–citrulline linkers ensure stability and efficacy of antibody–drug conjugates in mice

Fig. 1

Structures and plasma stability of cathepsin-responsive cleavable peptides. a VCit and EVCit-based ADC linkers. VCit linkers are unstable in mouse plasma due to susceptibility to the extracellular carboxylesterase Ces1c. This instability often triggers premature release of payload in circulation. This study presents that VCit-based tripeptide sequences with an acidic side chain such as EVCit are responsive to cathepsin-mediated cleavage but highly stable in mouse plasma. b Structures of pyrene-based small-molecule probes containing a VCit (1a), SVCit (1b), EVCit (1c), DVCit (1d), KVCit (1e) or HO-GVCit (1f) cleavable sequence. c Stability of probes (1a–f) in undiluted BALB/c mouse plasma at 37 °C. (1a) blue circle; (1b) orange triangle; (1c) green square; (1d) magenta hexagon; (1e) red inversed triangle; (1f) gray cross. EVCit and DVCit probes (1c, d) showed great plasma stability while highly responsive to cathepsin B-mediated cleavage (see Supplementary Fig. 2). All assays were performed in triplicate. Error bars represent s.e.m. and values in parentheses are 95% confidential intervals

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