抄録
Based on molecular mechanisms for various diseases, treatment of a patient with drugs that specifically normalize pathologic metabolisms occurring at the site of tissue injury has been focused attention. Since enzymes and bioactive peptides, such as peptide hormones, function extremely specifically even in vivo, they have been assumed to be excellent therapeutics. Recent progress in genetic engineering permits to produce sufficient amounts of human types of enzymes and bioactive peptides that can be used for medical treatment without any immunological complications. The technique of site-specific mutagenesis also permits to obtain protein-peptide drugs that are highly resistant to proteolysis. in vivo. Such a remarkable improvement in the technology of molecular biology seemed to open the new tactics for treating patients at molecular level. However, recent studies also revealed that these protein-peptide drugs are often ineffictive predominantly because of their unfavorable behavior in vivo, such as short half lives in the circulation and insufficient mobilization to their site (s) of action. The present work describes biological mechanisms by which the fates of enzymes and peptides in the circulation are determined, the theoretical background required for drug design by which in vivo behaviors of protein-peptide drugs can be controled to efficiently exhibit thier therapeutic actions. The new strategy for targeting enzymes and bioactive peptides by gene and protein engineering is also described.
