Phage display and PEGylation of therapeutic proteins.
With the success of the human genome project, the focus of life science research has shifted to the functional and structural analyses of proteins, such as disease proteomics and structural genomics. These novel approaches to the analyses of proteins, including newly identified ones, are expected to help in the identification and development of protein therapies for various diseases. Thus, disease proteomic-based drug discovery has a very high profile. Nevertheless, the use of bioactive proteins in the clinical setting is not straightforward because, in vivo, these proteins have a low stability and a pleiotropic action. To promote disease proteomic-based drug discovery and development, we have attempted to establish a system for creating functional mutant proteins (muteins) with the desired properties, and also to develop a site-specific polymer-conjugation system for further improving their therapeutic potency. These innovative protein-drug systems are discussed in this review.
Mukai
Yohei
Y
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoshioka
Yasuo
Y
Tsutsumi
Yasuo
Y
D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008403:Mass Screening; D009154:Mutation; D019151:Peptide Library; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011506:Proteins / Q000737:chemistry / Q000627:therapeutic use*; D040901:Proteomics; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000627:therapeutic use*
D015850:Interleukin-6; D019151:Peptide Library; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D011205:Povidone