Structure of slow-reacting substance of anaphylaxis from guinea-pig lung

Abstract

Slow-reacting substance of anaphylaxis (SRS-A) is a primary mediator of immediate-type hypersensitivity reactions, probably having a major bronchoconstrictor role in asthma. Although it was discovered some 40 years ago1 the structure has remained unknown. Major advances in purification technology2,3 have resulted in the preparation of chemically pure material, and the demonstration that SRS-A has a characteristic UV spectrum2 has enabled a correlation to be made between biological activity and a structural moiety in the molecule. Previous studies have indicated that SRS-A from guinea pig lung is derived from arachidonic acid4; data, based on the chemical and enzymatic destruction of biological activity, have indicated the presence of α-amino, carboxyl and thioether functions3. We now report the first spectroscopic (mass spectrometric) and analytical protein chemical data on intact SRS-A which allows us to define unequivocally the complete covalent structure of this immunologically generated material as the novel peptidolipid 5-hydroxy-6-cysteinyl glycinyl-7, 9, 11, 14-eicosatetraenoic acid. The structure determined is identical to that which we have assigned to the major non-immunologically generated slow-reacting substance (SRS) obtained from rat basophil leukaemia (RBL-1) cells5, but different from that of a recently synthesized chemical with SRS-like activity6 whose structure was modified from an earlier, incorrect structure of the natural product7.