A Less Toxic Heparin Antagonist--Low Molecular Weight Protamine

J. F. Liang^*, L. Zhen, L.-C. Chang, and V. C. Yang

College of Pharmacy, The University of Michigan, 428 Church str., Ann Arbor, MI 48109-1065, USA; fax: (734) 763-9772; E-mail: junfeng@umich.edu

^* To whom correspondence should be addressed.

Received April 23, 2002; Revision received May 18, 2002

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A new thirteen amino acid peptide, named low molecular weight protamine (LMWP), was obtained through the enzymatic digestion of native protamine. Both in vitro and in vivo results showed that LMWP fully maintained the heparin neutralization function of protamine but had much lower immunogenicity and antigenicity. Unlike protamine, neither LMWP nor LMWP/heparin complexes caused significant blood platelet aggregation in rats. These results suggest that LMWP can be used as a substitute for protamine for developing a new generation of nontoxic heparin antagonists.

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KEY WORDS: low molecular weight protamine, heparin neutralization, immunogenicity, platelet aggregation

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