Accession Number : ADA262909


Title :   Report for Office of the Chief of Naval Research Contract N00014-92-J-1695,


Corporate Author : OHIO STATE UNIV COLUMBUS


Personal Author(s) : Burke, Thomas G


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a262909.pdf


Report Date : Apr 1993


Pagination or Media Count : 6


Abstract : Pharmacological approaches to the optimization of the oxygen affinity of liposome-encapsulated hemoglobin (LEH), a potential blood replacement fluid, are being developed. LR16 and L35 are recently-synthesized drugs which are known to be potent modulators of the P50 of human hemoglobin (Lalezari et al, Biochemistry 29;1515-1523 (1990)). In this report we describe the synthesis of several related 2-methylpropionic acid-derived modifiers of human hemoglobin. Structural modifications to the LR16 molecule include an analogue containing the addition of a quaternary ammonium salt, as well as drugs containing an amino group, trifluoromethyl moieties, and fluorine substituents. A thiorea analogue was also synthesized. Several of the new compounds were found to be biologically-active when tested on human hemoglobin, the most potent compound shifting the P50 value of 200 uM human hemoglobin to 18mm Hg using a drug concentration of 2 mM. Analogues that exhibit both potency as well as low membrane permeability (i.e. high retentivity of drug within the liposomal particle) are being sought.


Descriptors :   *LIPOSOMES , *SYNTHESIS(CHEMISTRY) , *HEMOGLOBIN , MEMBRANES(BIOLOGY) , POTENCY , BLOOD SUBSTITUTES , BLOOD , DRUGS , PERFORMANCE(HUMAN) , BIOCHEMISTRY


Subject Categories : Biochemistry
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE