Crack Serial Sap Crystal Dashboard Design 2011 ##VERIFIED##
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Having identified and validated human CRP as a therapeutic target, we designed novel bis(phosphocholine)-alkanes as inhibitors of ligand binding by human CRP in vivo. These ligands for CRP were based on our knowledge of the 3D X-ray crystal structure of the CRP-phosphocholine complex (31) and our experience with miridesap, hexanoyl-bis(D-proline), the SAP inhibitor drug (72). We showed that bis(phosphocholine)-hexane (32) and bis(phosphocholine)-octane (unpublished) completely abrogated the enhancement of tissue damage caused by human CRP in the rat acute myocardial infarction model.
Having identified and validated human CRP as a therapeutic target, we designed novel bis(phosphocholine)-alkanes as inhibitors of ligand binding by human CRP in vivo. These ligands for CRP were based on our knowledge of the 3D X-ray crystal structure of the CRP-phosphocholine complex (31) and our experience with miridesap, hexanoyl-bis(D-proline), the SAP inhibitor drug (72). We showed that bis(phosphocholine)-hexane (32) and bis(phosphocholine)-octane (unpublished) completely abrogated the enhancement of tissue damage caused by human CRP in the rat acute myocardial infarction model. Binding of human CRP to these compounds inhibits CRP binding to other ligands, though it does not accelerate clearance of CRP from the circulation as miridesap does with human SAP. d2c66b5586