Of the 70-residue polypeptide human platelet factor 4, which binds heparin stoichiometrlcally, the C-terminal fragment 50-70 /Tc-3/ showed a reduction of the heparin induced prolongation of thrombin time /Deuel et al., Proc. Natl. Acad. Sei. USA., 74:2256, 1977/.
The arginine analog of the fragment 58-68 of Tc-3, which comprises the unique lysine rich region /Lys-Lys-Ile-Ile-Lys-Lys/, was ... [Show full abstract] prepared; Pro-Leu-Tyr-Arg-Arg-Ile-Ile-Arg-Arg-Leu-Leu-NH2. The aim of replacing of lyslne residues of the native molecule by arginine was to increase the interactions between the basic side chains of the peptide and SO3 - and/or COO- groups of heparin by introducing additional H-bridges and strengthening the ionic bonds. The new undecapeptide was synthesized by the standard solid phase method using Boc amino acids and dicyclo-hexylcarbodiimide condensation.
1 nmole /1.8/ug/ of synthetic peptide completely inhibits the action of 0.3 units of heparin which corresponde a heparin/peptide molecular ration of about 1:6.