著者

野村 渉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.10, pp.1223-1231, 2017 (Released:2017-10-01)

参考文献数

17

被引用文献数

1

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Interactions between bio-macromolecules such as proteins, DNA, and polysaccharides play pivotal roles in maintaining homeostasis in living systems. For elucidating the function of biomolecules, peptides are powerful tools, compared to native proteins, because of their lower molecular weights, compatibility with chemical modification, and predictability of interaction with the target molecules. These advantages enabled us to develop peptide-based functional molecules. However, for the purposes of controlling or regulating biomolecule functions, designing artificial proteins is also an effective approach. Not only rational protein design, but also directed molecular evolution, are now regarded as powerful methods for optimizing protein function. The interactions of proteins with bio-macromolecules are usually highly specific and show high affinity because of larger interaction surfaces as compared to small molecules or peptides. Thus, the use of proteins for designing biofunctional molecules is also important for wider applications in the biotechnology field. In this review, four topics will be discussed: 1) the development of fluorescently-labeled ligands for G protein-coupled receptors (GPCR), as well as bivalent ligands for GPCR imaging and function analysis, 2) the design and synthesis of gp41 trimer mimics as HIV-1 inhibitors or vaccines, 3) the development of a ZIP tag-probe system and its application to intracellular protein imaging, and 4) the functional analysis of sequence-specific DNA recombinase for expanding the scope of genome editing. The results of these studies indicate the importance of precision in the design of peptides or proteins for regulating bio-macromolecular interactions.

著者

野村 渉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.3, pp.405-414, 2015 (Released:2015-03-01)

参考文献数

79

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Artificial zinc finger proteins (ZFPs) consist of Cys2-His2-type modules composed of approximately 30 amino acids that adopt a ββα structure and coordinate a zinc ion. ZFPs recognizing specific DNA target sequences can substitute for the binding domains of various DNA-modifying enzymes to create designer nucleases, recombinases, and methylases with programmable sequence specificity. Enzymatic genome editing and modification can be applied to many fields of basic research and medicine. The recent development of new platforms using transcription activator-like effector (TALE) proteins or the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) system has expanded the range of possibilities for genome-editing technologies. These technologies empower investigators with the ability to efficiently knockout or regulate the functions of genes of interest. In this review, we discuss historical advancements in artificial ZFP applications and important issues that may influence the future of genome editing and engineering technologies. The development of artificial ZFPs has greatly increased the feasibility of manipulating endogenous gene functions through transcriptional control and gene modification. Advances in the ZFP, TALE, and CRISPR/Cas platforms have paved the way for the next generation of genome engineering approaches. Perspectives for the future of genome engineering are also discussed, including applications of targeting specific genomic alleles and studies in synthetic biology.