The minimal functional sequence of protamine.
Despite its nearly universal applications, protamine, a mixture of four major peptides with different sequences, is associated with clinically significant side effects. Through a well-designed enzyme digestion method, various low molecular weight protamine peptides were obtained. Among them, two low molecular weight protamine peptides with the same or even more potent heparin neutralization abilities as native protamine were identified through both in vitro and in vivo tests. In addition, in vivo experiments showed that compared to native protamine, these two low molecular weight protamine peptides were less toxic and would be safer for clinical use.
Liang
Jun Feng
JF
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
Yang
Victor C
VC
Vaynshteyn
Yekaterina
Y
D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011479:Protamines / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D011479:Protamines; D006493:Heparin