Molecular design, characterization and pharmacological activity of conjugates of protein proteinase inhibitors

Protein proteinase inhibitors have been used for the treatment and prophyla xis of a variety of severe disorders, causing by uncontrollable activation of serine proteinases. Besides, use of proteinase inhibitors for improving oral bioavailability of therapeutic peptides and proteins has gained consid er-able scientific interest. Therefore the development of delivery systems for protein proteinase inhibitors holds great therapeutic promise. This art icle reviews the investigations in which the attempts to control transport pattern and biodistribution of protein proteinase inhibitors by conjugating them with appropriate carriers were undertaken. A specific concept of desi gning the conjugates based on the structural, physico-chemical and enzymati c aspects was suggested It was demonstrated that the general approach is ap plicable to the various proteinase inhibitors, and significant and sustaine d specific pharmacological activity could be obtained by their conjugation.