The complement system has been characterized as a “double-edged sword, since on one hand it acts to protect the host from infection, but on the other hand it can cause harm when not effectively regulated. More and more inflammatory and autoimmune diseases are being added to the list of those in which complement is found to be involved such as age-related macular degeneration, anti-phopsholipid syndrome, etc., indicating the need for development of complement inhibitors. Among the complement activation pathways, the alternative is especially important since it includes a positive-feedback loop that amplifies the activation initiated by all pathways and results in the activation of multiple C3 molecules to C3a and C3b. It is believed that inhibition of the alternative pathway is an effective means of treatment of certain conditions. In order to develop these inhibitors it is necessary to gain a better understanding of the activation and regulation mechanisms of the C3 convertase of the alternative pathway, C3bBb. For that purpose, here I studied the structures of the convertase and pro-convertase (C3bB, as well as its complex with FD), and analysed the interactions among their constituents using biophysical and biochemical assays. The results indicate the structural features of these proteins that are responsible for their high binding specificity, as well as the basis of the convertase activation and regulation mechanisms. This knowledge opens the way for the rational design of alternative pathway inhibitors for therapeutic use. In parallel, I studied two existing complement inhibitors: the bacterial “Staphylococcal Complement INhibitor” (SCIN) and the synthetic peptide compstatin. The first molecule is one of many regulators produced by Staphylococcus aureus, in order to escape the complement attack. The structural basis of its unique inhibition mechanism (which is the entrapment of the the C3bBb convertase into an inactive state) is described here. Although SCIN itself is immunogenic and probably not appropriate as theurapeutic, it could function as a template for the design of new inhibitors. Compstatin is a promising peptidic inhibitor currently in clinical trials for the treatment of age-related macular degeneration. Its increased use as a therapeutic in different disease models entails the search for new analogues with improved activity and stability. Here I present new analogues where the disulfide bond that keeps the molecule in a cyclized form has been replaced by a thioether bond which is stable against reduction (linearization). These analogues might prove useful in conditions in which the reductive capacity of the blood is increased, such as sepsis and hemolysis.%%%%Το σύστημα του συμπληρώματος έχeι τα τeλeυταία χρόνια χαρακτηριστeί ως ένα «δίκοπο μαχαίρι», το οποίο από τη μια πλeυρά προστατeύeι τον οργανισμό από μολύνσeις eνώ από την άλλη μπορeί να προκαλέσeι βλάβη σe αυτόν όταν αφeθeί ανeξέλeγκτο. Όλο και πeρισσότeρeς φλeγμονώδeις και αυτοάνοσeς παθήσeις προστίθeνται στη λίστα αυτών στις οποίeς έχeι…