Peptidic Inhibitors of Serine Proteinases of Plant Origin

Abstract

Serine proteinases play important roles in many physiological processes and in consequence, when unbalanced, are responsible for numerous severe diseases. The most predominant mechanism of their control is the ubiquitous presence of their inhibitors. On the basis of their inhibition mode, serine proteinase inhibitors are classified into canonical (standard mechanism) inhibitors, serpins and non-canonical inhibitors. The best studied are inhibitors assigned to the first group. At least 18 canonical inhibitor families have been recognized. Inhibitors isolated from the seeds of Cucurbitaceae are small (around 30 amino acid residues), containing three disulfide brides. Some of them are characterized by a cyclic polypeptide backbone. Head-to-tail cyclization is also present in the smallest (14 amino acid residues) trypsin inhibitor isolated from sunflower seeds. All these potent inhibitors display well-defined, rigid structures and, unlike most proteins, are also resistant to denaturizing agents. Modifications introduced into the molecules of these low-molecular-mass inhibitors are well tolerated, retaining their tertiary structure and inhibitory activity. They are able to cross cell membranes and are the first examples of cyclic cell-penetrating peptides. Recent results obtained on plant peptidic inhibitors and discussed in this mini-review have proved that they are promising molecules for drug design.