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S Wrenn

Publications and source records attributed to S Wrenn.

5 recordsLinked to original sources
PubMed1992

Analogues of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor.

A series of aryl phosphoglyceride (3, 19-61) and bis-aryl phosphate (67-135) antagonists of platelet activating factor (PAF) were prepared. A group of four bifunctional phosphorus reagents (5a-c and 7) were developed that allowed the preparation of these aryl phosphates in which the position of aromatic substitution can be varied. These compounds were examined for their ability to inhibit PAF-induced platelet aggregation of rabbit platelets. Selected compounds were also evaluated for their ability to displace [3H]PAF from its receptor on rabbit platelets. These in vitro data were compared to similar data obtained for a number of known PAF antagonists. The compounds were evaluated in vivo, in both the mouse and rabbit, for their ability to prevent death induced by a lethal challenge of PAF. The relationships between the biological activity and the nature, lipophilicity, and position of substituents of the aromatic rings were studied. Compound 105 (CL 184005) has been selected to undergo further development as a potential therapeutic agent for the treatment of septic shock in man.

Animals↗
PubMed1978

Affinity purification of cardiac adenylate cyclase: dependence on prior hydrophobic resolution.

The interaction of cardiac adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] with a variety of nucleotide affinity resins was systematically investigated. None of these resins effectively bound the native, detergent-solubilized enzyme. However, after hydrophobic resolution on an uncharged resin consisting of long-chain alkyl groups linked to agarose via ether bonds, 40% of the adenylate cyclase activity biospecifically adsorbed to an ATP affinity resin. Gel filtration without detergent after hydrophobic chromatography demonstrated that the enzyme eluted in the identical position as the native enzyme chromatographed in the presence of detergent. This preparation almost completely biospecifically adsorbed to the same ATP-resin and was not eluted with 5 mM cyclic AMP, pyrophosphate, or GTP. If the GTP-washed immobilized enzyme was subsequently desorbed with ATP, then expected Gpp(NH)p (5'-guanylyliminodiphosphonate) sensitivity persisted. A preliminary purification scheme that resulted in an approximate 5000-fold increase in specific activity is presented. These observations indicate that a membrane-bound enzyme may appear to be intrinsically hydrophobic only by virtue of aggregation with other hydrophobic constituents and that prior separation of hydrophobic chromatography may permit such proteins to be fractionated subsequently by methods conventionally applied to hydrophilic proteins.

Adenosine Triphosphate↗