Anti-PD1 'SHR-1210' aberrantly targets pro-angiogenic receptors and this polyspecificity can be ablated by paratope refinement.

Monoclonal anti-programmed cell death 1 (PD1) antibodies are successful cancer therapeutics, but it is not well understood why individual antibodies should have idiosyncratic side-effects. As the humanized antibody SHR-1210 causes capillary hemangioma in patients, a unique toxicity amongst anti-PD1 antibodies, we performed human receptor proteome screening to identify nonspecific interactions that might drive angiogenesis. This screen identified that SHR-1210 mediated aberrant, but highly selective, low affinity binding to human receptors such as vascular endothelial growth factor receptor 2 (VEGFR2), frizzled class receptor 5 and UL16 binding protein 2 (ULBP2).

Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus.

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans.

Turnover-dependent covalent inactivation of Staphylococcus aureus coenzyme A-disulfide reductase by coenzyme A-mimetics: mechanistic and structural insights.

Disruption of the unusual thiol-based redox homeostasis mechanisms in Staphylococcus aureus represents a unique opportunity to identify new metabolic processes and new targets for intervention. Targeting uncommon aspects of CoASH biosynthetic and redox functions in S. aureus, the antibiotic CJ-15,801 has recently been demonstrated to be an antimetabolite of the CoASH biosynthetic pathway in this organism; CoAS-mimetics containing α,β-unsaturated sulfone and carboxyl moieties have also been exploited as irreversible inhibitors of S.

Immobilization of active human carboxylesterase 1 in biomimetic silica nanoparticles.

The encapsulation of proteins in biomimetic silica has recently been shown to successfully maintain enzymes in their active state. Organophosphate (OP) compounds are used as pesticides as well as potent chemical warfare nerve agents. Because these toxicants are life threatening, we sought to generate biomimetic silicas capable of responding to OPs.