Proteinase inhibition, immunoglobulin-binding proteins and a novel antimicrobial principle.
Recent work has demonstrated that a tripeptide derivative mimicking the active proteinase-binding site of cystatin C, a human cysteine proteinase inhibitor, can block growth of group A streptococci and replication of herpes simplex virus (HSV). In the case of HSV, intact cystatin C was also found to inhibit replication of the virus. Many streptococcal strains and HSV-infected cells produce immunoglobulin (Ig)-binding proteins, and a possible connection between such proteins and proteolytic activity was indicated by the finding that bacterial Ig-binding proteins also show affinity for proteinase inhibitors. The significance of these various observations is not clear, but available data suggest that proteinases play a role in vital microbial functions (e.g. viral replication) and may be utilized as targets for antimicrobial agents. The results discussed here also indicate that peptide derivatives based on the structure of proteinase inhibitors occurring in nature could be used as such agents.
Björck
L
L
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
D000595:Amino Acid Sequence; D055316:Cystatin C; D015891:Cystatins / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D029584:Prostatic Secretory Proteins; D018139:Simplexvirus / Q000502:physiology*; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development*; D014779:Virus Replication / Q000187:drug effects
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D008222:Lymphokines; D009842:Oligopeptides; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors; C062355:N-benzyloxycarbonyl-leucyl-valyl-glycine diazomethane