The Role of Serine in the Linkage of Heparin to Protein

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SUMMARY A number of commercial heparin preparations have been examined for the presence of amino acids. Heparin which had been prepared by use of mild methods essentially based on treat- ment with proteolytic enzymes, contained residual amino acids with serine as the main component. In some preparations serine was the only amino acid found in significant amounts. Samples prepared under more drastic conditions, including alkali extrac- tion and bleaching at elevated temperatures, contained only traces of amino acids. It is suggested that heparin occurs in the native state as a complex with protein and that the carbohydrate- protein linkage is similar to that of the chondroitin 4-sulfate- protein complex. dcknowledgments-We are indebted to Professor E. Jorpes, Karolinska Institutet, Stockholm, Mr. G. Linden, the Vitrum AB, Dr. H. H. R. Weber, and Dr. C. DeFiebre, Wilson Labora- tories, and to Dr. L. L. Coleman, the Upjohn Company, for providing the heparin samples. We are also grateful to the Vitrum AB and the Wilson Laboratories for the anticoagulant activity assays. We are grateful to Dr. A. Dorfman for stimulat- ing discussions and continued support throughout this work. We wish to thank Dr. M. B. Mathews for the molecular weight determinations and Miss M. L. Spach for skillful technical assist- ance.