title: Synthetic peptide inhibitors of complement serine proteases--II. Effects on hemolytic activity and production of C3a and C4a.
abstract: Synthetic peptides based on the amino acid sequence at the site of cleavage of C3 by classical and alternative pathway convertases were found to be poor inhibitors of hemolysis except at concns of 1 mM and higher. Synthetic peptides of a second type, based on the C-terminal sequence of antithrombin III, were more effective; the best among them caused significant inhibition of hemolysis at a concn of 5 microM. A hybrid peptide composed of the sequence at the site of cleavage of C4 by C1s attached to an antithrombin III sequence was selective, inhibiting the classical pathway with no effect on the alternative pathway at a concentration of 25 microM. Several of the antithrombin III peptides that inhibited hemolysis did not inhibit C4 activation by the classical pathway or activation of C3 by the classical and alternative pathways suggesting that these peptides affect hemolysis by inhibiting enzymes other than C1s and C4b2a of the classical pathway and C3bBb of the alternative pathway.
authors.affiliation: Biological Sciences Department, Monsanto Company, St. Louis, MO 63198.
authors.forename: C S
authors.initials: CS
authors.lastname: Schasteen
authors.forename: S A
authors.initials: SA
authors.lastname: McLafferty
authors.forename: G I
authors.initials: GI
authors.lastname: Glover
authors.forename: C Y
authors.initials: CY
authors.lastname: Han
authors.forename: J C
authors.initials: JC
authors.lastname: Mayden
authors.forename: W S
authors.initials: WS
authors.lastname: Liu
authors.forename: R P
authors.initials: RP
authors.lastname: Levine
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000990:Antithrombin III / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000096:biosynthesis* / Q000276:immunology; D015926:Complement C3a; D003181:Complement C4 / Q000096:biosynthesis*; D015934:Complement C4a; D006461:Hemolysis / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors
chemical_list: D003176:Complement C3; D003181:Complement C4; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D015926:Complement C3a; D015934:Complement C4a; D000990:Antithrombin III