Chemical Synthesis and Analysis of Short Peptides Containing Modified Arginine Residues

摘要

When designing peptide inhibitors of enzymes, including serine proteases, it is necessary to consider their resistance to enzymatic degradation. Very popular nowadays is modification of the peptide chain consisting of substitution of PI arginine residue (binding with SI pocket of the enzyme [1]) with compounds that are its mimetics. Owing to its specific structure, they have the potential to be more stable and less susceptible to enzymatic degradation. There is a wide range of known arginine mimetics, that incorporated into the peptide chain create strong inhibitors of serine proteases [2-5]. One of these compounds is 4-amidinobenzylamine (Amba). Many research groups were focused on synthesizing inhibitors of serine proteases (e.g. thrombin and urokinase) containing Amba in their structures [6-8]. Here we present results of the study verifying whether during coupling of 4-amidinobenzylamine to the C-terminus of the peptide chain, it is necessary to protect its amidino group, which hypothetically can be competitive for the free amino group. A set of analogues was synthesized using two various forms of Amba (Figure 1).