Inhibition of alternative pathway factor D by factor B-related synthetic hexapeptides.
Hexapeptides mimicking the partial amino acid sequence of factor B surrounding the bond that is cleaved by factor D have been synthesized. These peptides have been assessed for their ability to inhibit factor D enzymatic activity and for their susceptibility to serine proteases. The synthetic peptides were cleaved by bovine trypsin and C1s but not by alpha-thrombin and factor D. The peptides inhibited factor B cleavage and fluid-phase or cell-bound alternative pathway C3 convertase activation by factor D. Altogether, these results suggest that peptides analogous to factor B specifically inhibit factor D enzymatic activity. Thus, they constitute an interesting tool for study of alternative pathway activation and can be of use when attempting to manipulate this pathway, since factor D is an essential component for alternative pathway initiation and amplification.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003166:Complement Activating Enzymes / Q000037:antagonists & inhibitors*; D003167:Complement Activation / Q000187:drug effects*; D011415:Complement Factor B / Q000031:analogs & derivatives* / Q000378:metabolism; D011416:Complement Factor D / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003864:Depression, Chemical; D004792:Enzyme Precursors; D066298:In Vitro Techniques; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*
D004792:Enzyme Precursors; D010455:Peptides; D003166:Complement Activating Enzymes; D011416:Complement Factor D; D011415:Complement Factor B