Structural aspects and design of low-molecular-mass complement inhibitors.
We present a mini-review on the structure-based design of three promising complement inhibitors. Firstly, we review compstatin, a 13-residue cyclic peptide that binds to C3 and inhibits the cleavage of C3 to C3a and C3b. Secondly, we review a six-residue cyclic peptide that binds to C5aR and antagonizes the binding of C5a to its receptor C5aR. Finally, we review three small molecules that bind to Factor D and inhibit the enzymic action of Factor D, during which Factor D proteolytically cleaves Factor B in complex with C3 or C3b.
Morikis
D
D
Department of Chemical and Environmental Engineering, University of California at Riverside, 92521, USA. dmorikis@engr.ucr.edu
Lambris
J D
JD
D000818:Animals; D020134:Catalytic Domain; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D011416:Complement Factor D / Q000037:antagonists & inhibitors; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D003176:Complement C3; D003169:Complement Inactivator Proteins; D010456:Peptides, Cyclic; C111828:compstatin; D015926:Complement C3a; D003179:Complement C3b; C493488:CFD protein, human; D011416:Complement Factor D