Allosteric Modifiers of Hemoglobin: Potential Applications in Red Cell Storage and Liposome-Encepsulated Hemoglobin Development

摘要

The overall objective of the research program is to develop allosteric modifiers of hemoglobin. that are effective in vivo. The ability of a novel agent 02-50, a trifluoromethyl substituted analog of LRl6, was found to strongly modulate the P10 value of purified hemoglobin. 02-50 displayed activity greater than that of LRl6. However, the presence of human serum albumin (HSA) strongly modulated the pharmacological properties of LRl6 and 02-50 agents. Experiments with denatured HSA also revealed that the albumin interactions with LR-16 were not specific in nature and both LR-16 and 02-50 are lipophilic and capable of diffusing from LEH particles.