A structure-activity relationship study of platelet-activating factor
Technical Report
·
OSTI ID:6838850
Several analogues of platelet-activating factor (1-0-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine, PAF), an alkylglycerophospholipid that was found to be a mediator in Type I immediate hypersensitivity and also possessed potent hypotensive properties, were synthesized. These PAF analogues were evaluated in a qualitative structure-activity relationship study for their rabbit neutrophil degranulation properties and their antihypertensive properties in rats. Variations were made in each of the moieties attached to the three glycerol backbone carbons. Variation in sn-1-0-alkyl chain length from fourteen to nineteen carbons and introduction of one or two double bonds revealed that the 1-0-hexadecyl species of PAF was the most active analogue in this series in our assay systems. Substitution of various deoxyalkyl groups for the 2-0-acetyl moiety resulted in severely diminished bioactivities and no inhibition of rat plasma acetylhydrolase activity. Substitution of bulky trialkylammonium moieties for the trimethylammonium portion of the phosphocholine moiety resulted in an analogue (triethylammonium, 41) with reduced immediate hypersensitivity properties and 560% relative antihypertensive potency.
- Research Organization:
- North Carolina Univ., Chapel Hill (USA)
- DOE Contract Number:
- AC05-76OR00033
- OSTI ID:
- 6838850
- Report Number(s):
- DOE/OR/00033-T413; ON: DE88015646
- Country of Publication:
- United States
- Language:
- English
Similar Records
Activities of enzymes that metabolize platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in neutrophils and eosinophils from humans and the effect of a calcium ionophore
Development of a novel scintillation proximity radiommunoassay for platelet-activating factor measurement: Comparison with bioassay and GD/MS techniques
Enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a hypotensive and platelet-aggregating lipid
Journal Article
·
Thu Apr 29 00:00:00 EDT 1982
· Biochem. Biophys. Res. Commun.; (United States)
·
OSTI ID:6123850
Development of a novel scintillation proximity radiommunoassay for platelet-activating factor measurement: Comparison with bioassay and GD/MS techniques
Journal Article
·
Sun Dec 31 23:00:00 EST 1989
· Life Sciences; (USA)
·
OSTI ID:6705207
Enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a hypotensive and platelet-aggregating lipid
Journal Article
·
Mon Dec 31 23:00:00 EST 1979
· J. Biol. Chem.; (United States)
·
OSTI ID:6231033
Related Subjects
550200* -- Biochemistry
550300 -- Cytology
59 BASIC BIOLOGICAL SCIENCES
ALLERGY
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD CHEMISTRY
BLOOD PLATELETS
BODY FLUIDS
EVALUATION
MAMMALS
MATERIALS
METABOLIC ACTIVATION
PATHOLOGICAL CHANGES
RABBITS
STRUCTURE-ACTIVITY RELATIONSHIPS
VARIATIONS
VERTEBRATES
550300 -- Cytology
59 BASIC BIOLOGICAL SCIENCES
ALLERGY
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD CHEMISTRY
BLOOD PLATELETS
BODY FLUIDS
EVALUATION
MAMMALS
MATERIALS
METABOLIC ACTIVATION
PATHOLOGICAL CHANGES
RABBITS
STRUCTURE-ACTIVITY RELATIONSHIPS
VARIATIONS
VERTEBRATES