Cooper W John, Waters Marcey L
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Curr Opin Chem Biol. 2005 Dec;9(6):627-31. doi: 10.1016/j.cbpa.2005.10.015. Epub 2005 Oct 28.
The design of proteins and peptides as molecular receptors is a rapidly growing area of research. Two primary approaches have been utilized, involving the minimization of known protein binding motifs or the de novo design of binding pockets within well-folded protein structures. These approaches are complementary and help define the minimum requirements necessary for biomolecular recognition. Recent advances in this area include the design of cavities within helix bundles for the binding of anesthetics, the design of beta-hairpins for the recognition of nucleotides and oligonucleotides, the redesign of protein binding sites for unique ligands, and the design of mini-proteins via protein grafting for the recognition of proteins and DNA. These advances provide exciting new opportunities to develop novel biosensors, de novo designed catalysts, exogenously triggered synthetic signal transduction cascades, and novel approaches to therapeutic treatments.
将蛋白质和肽设计为分子受体是一个快速发展的研究领域。已经采用了两种主要方法,一种是将已知蛋白质结合基序最小化,另一种是在折叠良好的蛋白质结构中从头设计结合口袋。这些方法相互补充,有助于确定生物分子识别所需的最低要求。该领域的最新进展包括设计螺旋束内的空腔用于麻醉剂结合、设计β-发夹用于识别核苷酸和寡核苷酸、重新设计独特配体的蛋白质结合位点,以及通过蛋白质嫁接设计微型蛋白质用于识别蛋白质和DNA。这些进展为开发新型生物传感器、从头设计的催化剂、外源性触发的合成信号转导级联反应以及新的治疗方法提供了令人兴奋的新机会。