Lipopolysaccharide-specific acyloxyacyl hydrolase

dc.contributor.assigneeBoard of Regents, Univ. of Tex. Sys.
dc.creatorMunford, Robert S.
dc.creatorHall, Catherine L.
dc.date.accessioned2019-05-14T14:33:42Z
dc.date.available2019-05-14T14:33:42Z
dc.date.filed1991-05-07
dc.date.issued1991-05-07
dc.description.abstract" An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids from their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being being bound in turn to lipopolysaccharide glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight by gel exclusion chromatography between about 50,000 Daltons and about 70,000 Daltons, and a molecular weight by polyacrylamide gel electrophoresis with sodium dodecylsulphate, using reduced molecular weight standards, of approximately 54,000 to 60,000 Daltons. Altered bacterial lipopolysaccharide substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of lipopolysaccharide lipid A are produced. Since the structure of the lipid A moiety is highly conserved, acyloxyacyl hydrolase may act on lipopolysaccharide of many different pathogenic bacteria (for example Salmonella, Escherichia, Hemophilus, and Neisseria). Such altered bacterial lipopolysaccharide, having toxicity reduced more than immunostimulatory activity, may be therapeutically useful: (1) as vaccines to prevent Gram-negative bacterial diseases by inducing antibodies to lipopolysaccharide O-polysaccharide or R-core antigens, (2) as antidotes to treat or prevent Gram-negative bacterial sepsis (""septic shock""), or (3) as adjuvants to enhance formation of antibodies to other antigens. the acyloxyacyl hydrolase itself may be prophylactically or therapeutically useful to detoxify endogenous lipopolysaccharide in patients with Gram-negative bacterial diseases. The enzyme may also be used to remove toxic lipopolysaccharide from therapeutic injectants. "
dc.description.departmentBoard of Regents, University of Texas System
dc.identifier.applicationnumber7323679
dc.identifier.patentnumber5013661
dc.identifier.urihttps://hdl.handle.net/2152/74611
dc.identifier.urihttp://dx.doi.org/10.26153/tsw/1729
dc.publisherUnited States Patent and Trademark Office
dc.relation.ispartofUniversity of Texas Patents
dc.rights.restrictionOpen
dc.subject.cpcA61K39/02
dc.subject.cpcA61K39/0275
dc.subject.cpcC12N9/18
dc.subject.cpcC12P19/44
dc.subject.cpcY02A50/482
dc.subject.uspc424/94.61
dc.subject.uspc435/197
dc.subject.uspc435/84
dc.subject.uspc514/53
dc.subject.uspc514/54
dc.subject.uspc536/53
dc.titleLipopolysaccharide-specific acyloxyacyl hydrolase
dc.typePatent

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