​Overview:

• Cayman has made a SARS-CoV-2 (human) neutralizing recombinant antibody which disrupts the S1 RBD-ACE2 interaction.
• Surface plasmon resonance (SPR) was used to evaluate the recombinant neutralizing antibody's ability to block binding of SARS-CoV-2 S1 receptor binding domain (RBD) variants to human angiotensin-converting enzyme 2 (hACE2).  
• Cryo-electron microscopy (cryo-EM) single-particle analysis was used to determine the structure of intrinsically difficult-to-crystallize, >0.5 MDa SARS-CoV-2 spike:Fab complex.
  
• This case study shows the structure and conformational analysis of the SARS-CoV-2 spike glycoprotein trimer in complex with a Fab derived from a recombinant SARS-CoV-2 neutralizing antibody. Cayman's engineered recombinant antibody could effectively block the interaction of hACE2 with S1 RBD wild-type and Alpha variants better than that with the Beta variant.
• These structural results from cryo-EM and SPR studies could aid in the development of vaccines and therapeutics for the SARS-CoV-2 variants.
  

​Overview:

• Cayman’s Structural Biology service group worked with a client to perform crystallization studies that delivered multiple high-resolution crystal structures of LpxC, an enzyme involved in Gram-negative bacteria pathogenicity, bound with lead inhibitors.
  
• Thermal shift assay (TSA) protein formulation and cryoprotectant screening showed Mg²⁺ and tartrate to be effectively stabilizing for P. aeruginosa LpxC. Improved crystallization space and novel crystallization conditions were identified by TSA that enabled the co-crystallization of P. aeruginosa LpxC with inhibitor compounds.
  
• Crystal structures determined the key interactions of the inhibitors in the P. aeruginosa LpxC binding pocket. These findings led to the discovery of a prodrug with high solubility and rapid conversion to active drug upon i.v. administration to treat P. aeruginosa infections.
  
• The TSA-driven crystallization platform offered by Cayman enabled the client to rapidly advance their P. aeruginosa drug discovery program.
  

• Cayman Chemical’s structural biologists provided a drug discovery platform for the generation of small molecule autotaxin (ATX) inhibitors using their gene-to-structure pipeline.
• Crystal structures of mutant human ATX in complex with four structurally distinct ATX inhibitors are presented.
• Crystal structures confirm the unique mechanisms of inhibition displayed by ATX.
• A crystal structure with arachidonic acid (AA) represents the first ATX structure containing a substrate-bound secondary lysophosphatidic acid (LPA) binding site.
  
• This work enhanced our client’s drug discovery efforts, leading to a clinical candidate.