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Rapid discovery and development of serum-stable, selective, and high affinity peptide-based binders to protein targets are challenging. Angiotensin converting enzyme 2 (ACE2) has recently been identified as a cardiovascular disease biomarker and the primary receptor utilized by the severe acute respiratory syndrome coronavirus 2. In this study, we report the discovery of high affinity peptidomimetic binders to ACE2 via affinity selection-mass spectrometry (AS-MS). Multiple high affinity ACE2-binding peptides (ABP) were identified by selection from canonical and noncanonical peptidomimetic libraries containing 200 million members (dissociation constant,K_D = 19–123 nM). The most potent noncanonical ACE2 peptide binder, ABP N1 (K_D = 19 nM), showed enhanced serum stability in comparison with the most potent canonical binder, ABP C7 (K_D = 26 nM). Picomolar to low nanomolar ACE2 concentrations in human serum were detected selectively using ABP N1 in an enzyme-linked immunosorbent assay. The discovery of serum-stable noncanonical peptidomimetics like ABP N1 from a single-pass selection demonstrates the utility of advanced AS-MS for accelerated development of affinity reagents to protein targets.

 

Self-immolative polymers (SIPs) have been under development for over a decade, and efforts for their application followed shortly after their inception. One main area of application of SIPs is biomedicine, where they are used to construct devices and biosensors, develop new biotechnology abilities, or directly interface with the living system. Where traditional polymers are stable at room temperature, SIPs undergo rapid degradation when a labile capping group is removed, allowing SIPs to offer a highly unusual degradation profile compared with traditional polymers. This review summarizes the recent efforts to leverage the unique properties of SIPs for biomedical purposes, which are categorized into sensors, drug delivery, and biotechnology. By doing so, this review aims to stimulate future studies in this rapidly growing and promising area.