Increased inhibitory capacity of an anti-C5a complementary peptide following acetylation of N-terminal alanine.
Amino acids 37 to 53 (RAARISLGPRCIKAFTE) of C5a anaphylatoxin form an essential region for C5a function. To target this sequence, we generated a complementary peptide (ASGAPAPGPAGPLRPMF) designated PepA which has a potent inhibitory effect on C5a activity. By introducing an acetyl group at the N-terminal alanine of PepA, an acetylated form was generated which was designated AcPepA. The acetylation resulted in increased inhibition of C5a stimulation of neutrophils as determined by Ca influx. Furthermore, AcPepA partially inhibited the lethal shock induced in mice by intravenous administration of Candida albicans water-soluble mannoprotein-beta-glucan complex. In addition, local skin inflammation in rats caused by an anti-Crry monoclonal antibody was suppressed when AcPepA and the antibody were injected together, while PepA had little inhibitory capacity. The potent inhibitory capacity of AcPepA was also confirmed by a skin reaction of guinea pigs inoculated with recombinant human C5a together with AcPepA.
Okada
Noriko
N
Department of Biodefense Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Asai
Suzuka
S
Hotta
Aya
A
Miura
Noriko
N
Ohno
Naohito
N
Farkas
Imre
I
Hau
Lewis
L
Okada
Hidechika
H
D000107:Acetylation; D000409:Alanine / Q000737:chemistry*; D000818:Animals; D015936:Complement C5a / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006168:Guinea Pigs; D007249:Inflammation / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects
D010446:Peptide Fragments; D015936:Complement C5a; D000409:Alanine