Does crystallographic analysis reveal the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin?
The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.
Enteral Arg supplementation before sepsis significantly enhanced peritoneal macrophage phagocytic activity and reduced total bacterial counts in peritoneal lavage fluid. Arg administered before and after CLP seemed to have a synergistic effect on enhancing phagocytic activity and on bacterial clearance. However, IV Arg administration after CLP had no favorable effects on phagocytic activity or survival rates in rats with gut-derived sepsis.