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• W2593165792 abstract "In ancient times, natural extracts that derived mainly from plants and animals were utilized for medical or religious purposes. Even after starting the drug discovery and development in the realm of modern pharmacological sciences, the traditional medicines are still reasonably valued. Moreover, the modern approaches for drug discovery are appreciably supported by the resources and the accumulated knowledge of naturally occurring ligands and the offense- and defense-related substances. Among them, bioactive peptides, peptide toxins, and antibodies have been successfully applied in therapy due to their superior target selectivity. However, such biotherapeutics have middle to large molecular weights (>500 Da) in contrast to small molecular weight drugs. Size minimization is especially a concern for membrane permeability, stability in blood, antigenicity, and production costs. Biotherapeutic molecules have been engineered and further improved in terms of their affinity, stability and humanization for more than a decade to make them suitable for biotherapeutics. In this chapter, two approaches currently being used to improve biotherapeutics are overviewed: the size reduction of immunoglobulin-based biotherapeutics and the utilization of nonimmunoglobulin scaffolds. In both approaches, random peptide libraries are constructed based on each scaffold and screened for specific binders (polypeptides) with bioactivities of interest. Natural scaffolds that have been refined during long-term evolution are focused on. Some genes encoding offense/defense or reproduction-related proteins are known to undergo unusually rapid amino acid substitutions in the mature protein-coding regions, whereas the cysteine framework and α/β structures are conserved to maintain the molecular scaffold. This mode of evolution (called accelerated evolution) inspired the utilization of the gene as a template to construct a random peptide library for use for directed evolution in vitro. Screening and in vitro evolution technologies, including phage display, ribosome/mRNA/cDNA displays, the new technology “PERISS,” and in vitro compartmentalization, are also discussed." @default.
• W2593165792 created "2017-03-16" @default.
• W2593165792 creator A5022227076 @default.
• W2593165792 date "2017-01-01" @default.
• W2593165792 modified "2023-10-14" @default.
• W2593165792 title "Random Peptide Library for Ligand and Drug Discovery" @default.
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• W2593165792 doi "https://doi.org/10.1007/978-94-007-6452-1_2" @default.
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