CROSSLINKED HEMOGLOBINS

点击翻译按钮获取中文摘要

The scope of this project is the chemical development of oxygen carriers, and their screening and testing on kidney function. Specific aims include: 1) exploitment of the versatility of polyaspirin reagents for obtaining oxygen carriers with lower oxygen affinity, higher cooperativity and diminished urine elimination, 2) to search for controllable inter-molecular crosslinks of hemoglobin molecules, 3) to screen biological viability of the oxygen carriers by measuring retention time, urine elimination, acute and chronic renal effects. We will explore the use of di- and tri-aspirins for intramolecular crosslinks which will lower the oxygen affinity and decrease urine elimination; long carbon chains diaspirins, bis-maleimido and bis-alkylating agents will be used for producing controllable inter-molecular crosslinks. For obtaining hemoglobin octamers we will synthesize crosslinkers where two bifunctional reagents are joined by a branched carbon chain. Functional tests will characterize the thermodynamics of the intermediates of oxygenation in the oxygen carriers as compared to that of normal hemoglobin. This will give useful information for the engineering of oxygen carriers.