Flexizyme‐Mediated Genetic Reprogramming As a Tool for Noncanonical Peptide Synthesis and Drug Discovery

Noncanonical peptides occur frequently in Nature, and often display high bioactivity. However, the lack of tractable systems for the synthesis of diverse libraries of such peptides has thus far hampered their development as drugs. Genetic reprogramming techniques, in which noncanonical amino acids may be incorporated into peptides, have largely removed this limitation. This Concept article outlines the development of these techniques with an emphasis on drug discovery.     

Construction of a Live‐Attenuated HIV‐1 Vaccine through Genetic Code Expansion

A safe and effective vaccine against human immunodeficiency virus type 1 (HIV‐1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV‐1 replication, which entails the manipulation of essential HIV‐1 protein biosynthesis through unnatural amino acid (UAA*)‐mediated suppression of genome‐encoded blank codon. We successfully demonstrate that HIV‐1 replication can be precisely turned on and off in vitro.     

Initiation of Protein Synthesis with Non‐Canonical Amino Acids In Vivo

By transplanting identity elements into E. coli tRNA^fMet, we have engineered an orthogonal initiator tRNA (itRNA^Ty2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNA^Ty2 can initiate translation in vivo with aromatic non‐canonical amino acids (ncAAs) bearing diverse sidechains. Although the initial system suffered from low yields, deleting redundant copies of tRNA^fMet from the genome afforded an E. coli strain in which the efficiency of non‐canonical initiation equals elongation. With this improved system we produced a protein containing two distinct ncAAs at the first and second positions, an initial step towards producing completely unnatural polypeptides in vivo. This work provides a valuable tool to synthetic biology and demonstrates remarkable versatility of the E. coli translational machinery for initiation with ncAAs in vivo.     

面向天基引力波探测的时间延迟干涉技术

时间延迟干涉技术(Time-delay?Interferometry,TDI)对中国引力波探测项目及其它天基激光精密测量任务具有重要的参考价值.在天基引力波探测任务中,需利用激光干涉仪对无拖曳检验质量块间实现十皮米量级的位移测量精度.其中,激光源频率噪声和时钟频率噪声是两项主要噪声.在欧洲主导的LISA(Laser?I...     

竖向不规则结构抗震性能研究现状及其在设计规范中的应用

结构竖向不规则布置是导致结构地震损伤破坏的主要原因之一.介绍了建筑结构沿竖向的强度、刚度和质量不规则布置的定义、不规则的主要内容及其在地震作用下损伤破坏的特点;总结回归了钢筋混凝土竖向不规则结构地震反应需求的研究现状以及国际上典型的结构设计规范中结构竖向不规则条款的限定.针对竖向不规则结构目前的研究现状,提出了今后值得进一步加强研究的方向.