Synthetic peptides with the biological activities and specificity of human C3a anaphylatoxin.
Two peptides identical to the COOH-terminal sequence of human C3a anaphylatoxin and two analogs were synthesized by the solid-phase method and tested for biological activity. The synthetic COOH-terminal octapeptide, C3a-(70-77) or Ala-Ser-His-Leu-Gly-Leu-Ala-Arg, caused contraction of guinea pig ileum and uterus, release of vasoactive amines from rat mast cells, and increased vascular permeability in guinea pig and human skin. On a molar basis, the synthetic octapeptide possessed 1-2% of the biological activities of C3a and specifically desensitized smooth muscle to stimulation by C3a. Like natural C3a, the synthetic C3a=(70-77) was inactivated by digestion with carboxypeptidase B [peptidyl-L-lysine(-L-arginine) hydrolase, EC 3.4.12.3], which removed the essential COOH-terminal arginine. A synthetic nonapeptide [C3a-(70-77)-Gly], containing a glycyl instead of an arginyl COOH terminus, was approximately 1% as active as the octapeptide when assayed with smooth muscle. The COOH-terminal 13-residue peptide of C3a, C3a-(65-77), was equal in activity to C3a=(70-77); similarly, C3a-(65-77)-Gly expressed the same activity as C3a-(70-77)Gly. It is concluded that both the biological specificity and the activity of human C3a anaphylatoxin are determined by eight or fewer residues located at the COOH terminus of the natural protein. However, expression of full activity requires additional groups and the secondary conformational integrity of the C3a molecule.
D000595:Amino Acid Sequence; D000706:Anaphylatoxins / Q000494:pharmacology; D001681:Biological Assay; D002199:Capillary Permeability / Q000187:drug effects; D003176:Complement C3; D003165:Complement System Proteins; D005260:Female; D007082:Ileum; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus
D000706:Anaphylatoxins; D003176:Complement C3; D009842:Oligopeptides; D010455:Peptides; D012701:Serotonin; D003165:Complement System Proteins
J Immunol. 1976 Nov;117(5 Pt 1):1688-94
1002996
J Biol Chem. 1975 Feb 25;250(4):1472-8
803505
Clin Exp Immunol. 1972 May;11(1):13-20
4114148
J Clin Invest. 1970 Dec;49(12):2427-36
4098172
J Exp Med. 1968 Feb 1;127(2):371-86
4383923
J Biol Chem. 1975 Feb 25;250(4):1479-83
234458
J Am Chem Soc. 1973 May 30;95(11):3757-63
4708381
Annu Rev Biochem. 1975;44:697-724
1094920
J Immunol. 1976 Sep;117(3):990-5
956663
J Biol Chem. 1975 Nov 10;250(21):8293-301
1238393