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Dr. Toby Passioura Prof. Dr. Hiroaki Suga 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(21):6530-6536
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. 相似文献
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Nanxi Wang Dr. Yue Li Dr. Wei Niu Dr. Ming Sun Dr. Ronald Cerny Prof. Qingsheng Li Prof. Jiantao Guo 《Angewandte Chemie (International ed. in English)》2014,53(19):4867-4871
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. 相似文献
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Jeffery M. Tharp Omer Ad Kazuaki Amikura Fred R. Ward Emma M. Garcia Jamie H. D. Cate Alanna Schepartz Dieter Sll 《Angewandte Chemie (International ed. in English)》2020,59(8):3122-3126
By transplanting identity elements into E. coli tRNAfMet, we have engineered an orthogonal initiator tRNA (itRNATy2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNATy2 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 tRNAfMet 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. 相似文献
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