Synthetic peptides derived from the sequence of human C-reactive protein inhibit the enzymatic activities of human leukocyte elastase and human leukocyte cathepsin G.

Peptides derived from the primary sequence of the acute phase reactant C-reactive protein (CRP) are shown to inhibit in vitro the enzymatic activities of human leukocyte elastase (hLE) and human leukocyte cathepsin G (hCG), which are associated with tissue damage occurring in the course of several chronic inflammatory conditions. CRP-derived peptides were synthesized based on their sequence similarity to domains within the natural inhibitors of hLE and hCG. The octapeptide Val89-Thr-Val-Ala-Pro-Val-His-Ile96 (CRP 89-96) is shown to inhibit hLE and hCG to a larger extent than peptides of similar chain lengths corresponding to the active sites of their natural inhibitors, alpha 1-protease inhibitor and alpha-antichymotrypsin, respectively. Several additional peptides containing this core sequence were synthesized and shown to be inhibitors, in contrast to peptides derived from other regions of CRP as well as the intact protein, which are totally inactive. The inhibitory capability of CRP-derived peptides, which may be generated in vivo by neutrophil-mediated proteolysis as part of a complex regulatory homeostatic mechanism, may now be used as a basis for the design of novel therapeutic substances. The present finding may shed some light on the enigmatic physiological functions of CRP.