Noncanonical Amino Acids in the Interrogation of Cellular Protein Synthesis (original) (raw)

ArticleAugust 4, 2011

Noncanonical Amino Acids in the Interrogation of Cellular Protein Synthesis

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Cite this: Acc. Chem. Res. 2011, 44, 9

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Copyright © 2011 American Chemical Society

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Proteins in living cells can be made receptive to bioorthogonal chemistries through metabolic labeling with appropriately designed noncanonical amino acids (ncAAs). In the simplest approach to metabolic labeling, an amino acid analog replaces one of the natural amino acids specified by the protein’s gene (or genes) of interest. Through manipulation of experimental conditions, the extent of the replacement can be adjusted. This approach, often termed residue-specific incorporation, allows the ncAA to be incorporated in controlled proportions into positions normally occupied by the natural amino acid residue. For a protein to be labeled in this way with an ncAA, it must fulfill just two requirements: (i) the corresponding natural amino acid must be encoded within the sequence of the protein at the genetic level, and (ii) the protein must be expressed while the ncAA is in the cell.

Because this approach permits labeling of proteins throughout the cell, it has enabled us to develop strategies to track cellular protein synthesis by tagging proteins with reactive ncAAs. In procedures similar to isotopic labeling, translationally active ncAAs are incorporated into proteins during a “pulse” in which newly synthesized proteins are tagged. The set of tagged proteins can be distinguished from those made before the pulse by bioorthogonally ligating the ncAA side chain to probes that permit detection, isolation, and visualization of the labeled proteins.

Noncanonical amino acids with side chains containing azide, alkyne, or alkene groups have been especially useful in experiments of this kind. They have been incorporated into proteins in the form of methionine analogs that are substrates for the natural translational machinery. The selectivity of the method can be enhanced through the use of mutant aminoacyl tRNA synthetases (aaRSs) that permit incorporation of ncAAs not used by the endogenous biomachinery. Through expression of mutant aaRSs, proteins can be tagged with other useful ncAAs, including analogs that contain ketones or aryl halides. High-throughput screening strategies can identify aaRS variants that activate a wide range of ncAAs.

Controlled expression of mutant synthetases has been combined with ncAA tagging to permit cell-selective metabolic labeling of proteins. Expression of a mutant synthetase in a portion of cells within a complex cellular mixture restricts labeling to that subset of cells. Proteins synthesized in cells not expressing the synthetase are neither labeled nor detected. In multicellular environments, this approach permits the identification of the cellular origins of labeled proteins.

In this Account, we summarize the tools and strategies that have been developed for interrogating cellular protein synthesis through residue-specific tagging with ncAAs. We describe the chemical and genetic components of ncAA-tagging strategies and discuss how these methods are being used in chemical biology.

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  1. Edward D. Badding, Elijah N. Kissman, Stefan V. Velculescu, Michelle C. Y. Chang. Discovery of a Structurally Distinct Acetylenase in the Biosynthesis of Mangotoxin. Journal of the American Chemical Society 2026, Article ASAP.
  2. Raphael J. Turra, Satoru Horiya, Mahesh Neralkar, Jennifer K. Bailey, Timothy J. Walsh, Viktor Horvath, Isaac J. Krauss. Systematic Profiling of Peptide Substrate Specificity in N-Terminal Processing by Methionine Aminopeptidase Using mRNA Display and an Unnatural Methionine Analogue. ACS Chemical Biology 2026, 21 (2) , 263-273. https://doi.org/10.1021/acschembio.5c00680
  3. Teng Yuan, Qi Tang, Kelton Radefeld, Xiaohan Ye, Chuan Shan, Kai Zhao, Jaclyn Bredenkamp, Peter Y. Zavalij, Xiaodong Shi. Facile Asymmetric Synthesis of α,α-Disubstituted Amino Acid Derivatives with Gold Redox Catalysis Using a Chiral Auxiliary. ACS Catalysis 2025, 15 (17) , 14845-14852. https://doi.org/10.1021/acscatal.5c02965
  4. Žana Marin, Claudia Lacombe, Simindokht Rostami, Arshia Arasteh Kani, Andrea Borgonovo, Monika Cserjan-Puschmann, Jürgen Mairhofer, Gerald Striedner, Birgit Wiltschi. Residue-Specific Incorporation of Noncanonical Amino Acids in Auxotrophic Hosts: Quo Vadis?. Chemical Reviews 2025, 125 (10) , 4840-4932. https://doi.org/10.1021/acs.chemrev.4c00280
  5. Chiara De Faveri, Jordan M. Mattheisen, Thomas P. Sakmar, Irene Coin. Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies. Chemical Reviews 2024, 124 (22) , 12498-12550. https://doi.org/10.1021/acs.chemrev.4c00181
  6. Briana R. Lino, Sean J. Williams, Michelle E. Castor, James A. Van Deventer. Reaching New Heights in Genetic Code Manipulation with High Throughput Screening. Chemical Reviews 2024, 124 (21) , 12145-12175. https://doi.org/10.1021/acs.chemrev.4c00329
  7. James A. R. Tilden, Evan A. Doud, Hayden R. Montgomery, Heather D. Maynard, Alexander M. Spokoyny. Organometallic Chemistry Tools for Building Biologically Relevant Nanoscale Systems. Journal of the American Chemical Society 2024, 146 (44) , 29989-30003. https://doi.org/10.1021/jacs.4c07110
  8. Vera Wanka, Maximilian Fottner, Marko Cigler, Kathrin Lang. Genetic Code Expansion Approaches to Decipher the Ubiquitin Code. Chemical Reviews 2024, 124 (20) , 11544-11584. https://doi.org/10.1021/acs.chemrev.4c00375
  9. Wei Niu, Jiantao Guo. Cellular Site-Specific Incorporation of Noncanonical Amino Acids in Synthetic Biology. Chemical Reviews 2024, 124 (18) , 10577-10617. https://doi.org/10.1021/acs.chemrev.3c00938
  10. Kosuke Dodo, Katsumasa Fujita, Mikiko Sodeoka. Raman Spectroscopy for Chemical Biology Research. Journal of the American Chemical Society 2022, 144 (43) , 19651-19667. https://doi.org/10.1021/jacs.2c05359
  11. Ryan McBerney, Jonathan P. Dolan, Emma E. Cawood, Michael E. Webb, W. Bruce Turnbull. Bioorthogonal, Bifunctional Linker for Engineering Synthetic Glycoproteins. JACS Au 2022, 2 (9) , 2038-2047. https://doi.org/10.1021/jacsau.2c00312
  12. Emma K. Edelstein, Danica A. Rankic, Caroline C. Dudley, Spencer E. McMinn, Donovon A. Adpressa. Synthesis of Proline Analogues via Rh-Catalyzed Asymmetric Conjugate Addition. ACS Catalysis 2021, 11 (2) , 743-749. https://doi.org/10.1021/acscatal.0c04648
  13. Enkang Zhang, Yilong Shi, Jiahuai Han, Shoufa Han. Organelle-Directed Metabolic Glycan Labeling and Optical Tracking of Dysfunctional Lysosomes Thereof. Analytical Chemistry 2020, 92 (22) , 15059-15068. https://doi.org/10.1021/acs.analchem.0c03029
  14. Yun Hu, Jessica M. Roberts, Henry R. Kilgore, Amirah S. Mat Lani, Ronald T. Raines, Jennifer M. Schomaker. Triple, Mutually Orthogonal Bioorthogonal Pairs through the Design of Electronically Activated Sulfamate-Containing Cycloalkynes. Journal of the American Chemical Society 2020, 142 (44) , 18826-18835. https://doi.org/10.1021/jacs.0c06725
  15. Sarah L. Perry, Charles E. Sing. 100th Anniversary of Macromolecular Science Viewpoint: Opportunities in the Physics of Sequence-Defined Polymers. ACS Macro Letters 2020, 9 (2) , 216-225. https://doi.org/10.1021/acsmacrolett.0c00002
  16. Fangfang Wang, Hong Pan, Xiangjie Yao, Huamei He, Lanlan Liu, Yingmei Luo, Haimei Zhou, Mingbin Zheng, Renli Zhang, Yifan Ma, Lintao Cai. Bioorthogonal Metabolic Labeling Utilizing Protein Biosynthesis for Dynamic Visualization of Nonenveloped Enterovirus 71 Infection. ACS Applied Materials & Interfaces 2020, 12 (3) , 3363-3370. https://doi.org/10.1021/acsami.9b17412
  17. Larisa M. Dedkova, Sidney M. Hecht. Expanding the Scope of Protein Synthesis Using Modified Ribosomes. Journal of the American Chemical Society 2019, 141 (16) , 6430-6447. https://doi.org/10.1021/jacs.9b02109
  18. Shengxi Chen, Xun Ji, Mingxuan Gao, Larisa M. Dedkova, Sidney M. Hecht. In Cellulo Synthesis of Proteins Containing a Fluorescent Oxazole Amino Acid. Journal of the American Chemical Society 2019, 141 (14) , 5597-5601. https://doi.org/10.1021/jacs.8b12767
  19. Johnathan C. Maza, Daniel L. V. Bader, Lifeng Xiao, Alan M. Marmelstein, Daniel D. Brauer, Adel M. ElSohly, Matthew J. Smith, Shane W. Krska, Craig A. Parish, Matthew B. Francis. Enzymatic Modification of N-Terminal Proline Residues Using Phenol Derivatives. Journal of the American Chemical Society 2019, 141 (9) , 3885-3892. https://doi.org/10.1021/jacs.8b10845
  20. Bhaskar Bhushan, Yuya A. Lin, Martin Bak, Anuchit Phanumartwiwath, Nan Yang, Matthew K. Bilyard, Tomonari Tanaka, Kieran L. Hudson, Lukas Lercher, Monika Stegmann, Shabaz Mohammed, Benjamin G. Davis. Genetic Incorporation of Olefin Cross-Metathesis Reaction Tags for Protein Modification. Journal of the American Chemical Society 2018, 140 (44) , 14599-14603. https://doi.org/10.1021/jacs.8b09433
  21. Wes Brown, Jihe Liu, Alexander Deiters. Genetic Code Expansion in Animals. ACS Chemical Biology 2018, 13 (9) , 2375-2386. https://doi.org/10.1021/acschembio.8b00520
  22. Jessica T. Stieglitz, Haixing P. Kehoe, Ming Lei, James A. Van Deventer. A Robust and Quantitative Reporter System To Evaluate Noncanonical Amino Acid Incorporation in Yeast. ACS Synthetic Biology 2018, 7 (9) , 2256-2269. https://doi.org/10.1021/acssynbio.8b00260
  23. Jan-Erik Hoffmann, Dmytro Dziuba, Frank Stein, Carsten Schultz. A Bifunctional Noncanonical Amino Acid: Synthesis, Expression, and Residue-Specific Proteome-wide Incorporation. Biochemistry 2018, 57 (31) , 4747-4752. https://doi.org/10.1021/acs.biochem.8b00397
  24. Yingkai Liang, Linqing Li, Rebecca A. Scott, and Kristi L. Kiick . 50th Anniversary Perspective: Polymeric Biomaterials: Diverse Functions Enabled by Advances in Macromolecular Chemistry. Macromolecules 2017, 50 (2) , 483-502. https://doi.org/10.1021/acs.macromol.6b02389
  25. Zefan Li, Yuntao Zhu, Yuting Sun, Ke Qin, Weibing Liu, Wen Zhou, and Xing Chen . Nitrilase-Activatable Noncanonical Amino Acid Precursors for Cell-Selective Metabolic Labeling of Proteomes. ACS Chemical Biology 2016, 11 (12) , 3273-3277. https://doi.org/10.1021/acschembio.6b00765
  26. Kenneth E. Schwieter and Jeffrey N. Johnston . On-Demand Complex Peptide Synthesis: An Aspirational (and Elusive?) Goal for Peptide Synthesis. Journal of the American Chemical Society 2016, 138 (43) , 14160-14169. https://doi.org/10.1021/jacs.6b08663
  27. Kimberly C. Clarke and L. Andrew Lyon . Microgel Surface Modification with Self-Assembling Peptides. Macromolecules 2016, 49 (15) , 5366-5373. https://doi.org/10.1021/acs.macromol.6b01497
  28. Paul B. Lawrence, Wendy M. Billings, McKenzie B. Miller, Brijesh K. Pandey, Andrew R. Stephens, Minnie I. Langlois, and Joshua L. Price . Conjugation Strategy Strongly Impacts the Conformational Stability of a PEG-Protein Conjugate. ACS Chemical Biology 2016, 11 (7) , 1805-1809. https://doi.org/10.1021/acschembio.6b00349
  29. Heather E. Murrey, Joshua C. Judkins, Christopher W. am Ende, T. Eric Ballard, Yinzhi Fang, Keith Riccardi, Li Di, Edward R. Guilmette, Joel W. Schwartz, Joseph M. Fox, and Douglas S. Johnson . Systematic Evaluation of Bioorthogonal Reactions in Live Cells with Clickable HaloTag Ligands: Implications for Intracellular Imaging. Journal of the American Chemical Society 2015, 137 (35) , 11461-11475. https://doi.org/10.1021/jacs.5b06847
  30. Lu Wei, Yihui Shen, Fang Xu, Fanghao Hu, Jamie K. Harrington, Kimara L. Targoff, and Wei Min . Imaging Complex Protein Metabolism in Live Organisms by Stimulated Raman Scattering Microscopy with Isotope Labeling. ACS Chemical Biology 2015, 10 (3) , 901-908. https://doi.org/10.1021/cb500787b
  31. Nathan A. Carter and Tijana Zarkovic Grove . Repeat-Proteins Films Exhibit Hierarchical Anisotropic Mechanical Properties. Biomacromolecules 2015, 16 (3) , 706-714. https://doi.org/10.1021/bm501578j
  32. Hidetoshi Teramoto and Katsura Kojima . Production of Bombyx mori Silk Fibroin Incorporated with Unnatural Amino Acids. Biomacromolecules 2014, 15 (7) , 2682-2690. https://doi.org/10.1021/bm5005349
  33. Kathrin Lang and Jason W. Chin . Cellular Incorporation of Unnatural Amino Acids and Bioorthogonal Labeling of Proteins. Chemical Reviews 2014, 114 (9) , 4764-4806. https://doi.org/10.1021/cr400355w
  34. David M. Patterson, Lidia A. Nazarova, and Jennifer A. Prescher . Finding the Right (Bioorthogonal) Chemistry. ACS Chemical Biology 2014, 9 (3) , 592-605. https://doi.org/10.1021/cb400828a
  35. Kathrin Lang, Jason W. Chin. Bioorthogonal Reactions for Labeling Proteins. ACS Chemical Biology 2014, 9 (1) , 16-20. https://doi.org/10.1021/cb4009292
  36. Feng Wang, Andrea Gomez-Escudero, Rajasekhar R. Ramireddy, Gladys Murage, S. Thayumanavan, and Richard W. Vachet . Electrostatic Control of Peptide Side-Chain Reactivity Using Amphiphilic Homopolymer-Based Supramolecular Assemblies. Journal of the American Chemical Society 2013, 135 (38) , 14179-14188. https://doi.org/10.1021/ja404940s
  37. David M. Patterson, Lidia A. Nazarova, Bryan Xie, David N. Kamber, and Jennifer A. Prescher . Functionalized Cyclopropenes As Bioorthogonal Chemical Reporters. Journal of the American Chemical Society 2012, 134 (45) , 18638-18643. https://doi.org/10.1021/ja3060436
  38. Frank Truong, Tae Hyeon Yoo, Thomas J. Lampo, and David A. Tirrell . Two-Strain, Cell-Selective Protein Labeling in Mixed Bacterial Cultures. Journal of the American Chemical Society 2012, 134 (20) , 8551-8556. https://doi.org/10.1021/ja3004667
  39. David E. Mortenson, Kenneth A. Satyshur, Ilia A. Guzei, Katrina T. Forest, and Samuel H. Gellman . Quasiracemic Crystallization as a Tool To Assess the Accommodation of Noncanonical Residues in Nativelike Protein Conformations. Journal of the American Chemical Society 2012, 134 (5) , 2473-2476. https://doi.org/10.1021/ja210045s
  40. Kaiyu Wu, Suji Lee, Raquel Martinez-Serra, Lanyue Zhang, Steven Lynham, Karl Peter Giese. Low concentrations of amyloid-beta oligomers induce synaptogenesis characteristic for mild cognitive impairment and alter the de novo proteome. Translational Psychiatry 2026, 16 (1)https://doi.org/10.1038/s41398-026-03905-x
  41. Qiao Ran, Siyue Huang, Xiang David Li, Chaogu Zheng. Integrating MACSPI and SILAC for Neuron Type-specific Proteomics in Caenorhabditis elegans. Molecular & Cellular Proteomics 2026, 25 (4) , 101545. https://doi.org/10.1016/j.mcpro.2026.101545
  42. Kaitlyn Toy, Jenna N. Beyer, George M. Burslem. Chemical biology approaches for protein tagging in mammalian cells. Trends in Biochemical Sciences 2026, 51 (3) , 275-287. https://doi.org/10.1016/j.tibs.2025.12.004
  43. Sayali A. Mulay, Tatiana A. Vishnivetskaya, Leah H. Hochanadel, Dawn M. Klingeman, Karen G. Lloyd, Dale A. Pelletier, Mircea Podar, . BONCAT-Live for isolation and cultivation of active environmental bacteria. mBio 2025, 16 (11)https://doi.org/10.1128/mbio.02389-25
  44. Eva D. C. George Matlalcuatzi, Thomas Bakkum, Pooja S. Thomas, Stephan Hacker, Bogdan I. Florea, Bastienne Vriesendorp, Daniel E. Rozen, Sander I. van Kasteren, . Using BONCAT to dissect the proteome of S. aureus persisters. mSphere 2025, 10 (9)https://doi.org/10.1128/msphere.00431-25
  45. Josseline Ramos-Figueroa, Haoqian Liang, Wilfred A. van der Donk. Substrate recognition by a peptide-aminoacyl-tRNA ligase. Proceedings of the National Academy of Sciences 2025, 122 (12)https://doi.org/10.1073/pnas.2423858122
  46. . Direct quantification of cell type-specific proteins using Luminex assays with TurboID-labeled cells and tissues. 2025, 89-103. https://doi.org/10.1016/bs.mcb.2025.03.001
  47. . Repurposing branched chain amino acid aminotransferase in the chemoenzymatic synthesis of azacyclic noncanonical amino acids. 2025, 135-145. https://doi.org/10.1016/bs.mie.2025.08.019
  48. Yeojin Ko, Tae Wan Kim, Jong-il Choi. Evaluation of Docking Simulation Platforms for Predicting Incorporation Efficiency of Non-Canonical Amino Acids. KSBB Journal 2024, 39 (4) , 128-135. https://doi.org/10.7841/ksbbj.2024.39.4.128
  49. Jinchao Lou, Christelle F. Ancajas, Yue Zhou, Nicolas S. Lane, Todd B. Reynolds, Michael D. Best. Probing Glycerolipid Metabolism using a Caged Clickable Glycerol‐3‐Phosphate Probe. ChemBioChem 2024, 25 (18)https://doi.org/10.1002/cbic.202300853
  50. Min Hao, Xinyu Ling, Yi Sun, Xue Wang, Wenzhe Li, Liying Chang, Zhiying Zeng, Xiaomeng Shi, Mengxiao Niu, Liangyi Chen, Tao Liu. Tracking endogenous proteins based on RNA editing-mediated genetic code expansion. Nature Chemical Biology 2024, 20 (6) , 721-731. https://doi.org/10.1038/s41589-023-01533-w
  51. Tsung-Han Chao, Xiangyu Wu, Yu Fu, Licheng Yang, Hans Renata. Harnessing transaminases to construct azacyclic non-canonical amino acids. Nature Synthesis 2024, 3 (5) , 662-669. https://doi.org/10.1038/s44160-024-00514-8
  52. Zalina T. Gugkaeva, Maria P. Stukalova, Alexander F. Smol'yakov, Alan T. Tsaloev, Victor I. Maleev, Vladimir A. Larionov. Asymmetric Metal‐Templated Approach to Amino Acids with a CF 3 ‐Containing 3,2’‐Pyrrolidinyl Spirooxindole Core via a Michael/Mannich [3+2]‐Cycloaddition Reaction. Advanced Synthesis & Catalysis 2024, 366 (5) , 1205-1211. https://doi.org/10.1002/adsc.202301214
  53. Jung Min Kim, Jinho Jung. Highly chromophoric fluorescent‐labeled methionyl‐initiator tRNAs applicable in living cells. Biotechnology Journal 2024, 19 (3)https://doi.org/10.1002/biot.202300579
  54. Wei Huang, Scott T. Laughlin. Cell-selective bioorthogonal labeling. Cell Chemical Biology 2024, 31 (3) , 409-427. https://doi.org/10.1016/j.chembiol.2023.09.010
  55. Xiao-xi Guo, Su An, Fan Bao, Tian-rui Xu. Challenges and Perspectives in Target Identification and Mechanism Illustration for Chinese Medicine. Chinese Journal of Integrative Medicine 2023, 29 (7) , 644-654. https://doi.org/10.1007/s11655-023-3629-9
  56. Jordi C.J. Hintzen, Jasmin Mecinović. Synthetic cysteine-based tools for probing protein posttranslational modifications. Tetrahedron Letters 2023, 124 , 154602. https://doi.org/10.1016/j.tetlet.2023.154602
  57. Kai-Kai Tian, Zhi-Gang Qian, Xiao-Xia Xia. Synthetic biology-guided design and biosynthesis of protein polymers for delivery. Advanced Drug Delivery Reviews 2023, 194 , 114728. https://doi.org/10.1016/j.addr.2023.114728
  58. Yun‐Nam Choi, Namjin Cho, Kanghun Lee, Da‐ae Gwon, Jeong Wook Lee, Joongoo Lee. Programmable Synthesis of Biobased Materials Using Cell‐Free Systems. Advanced Materials 2023, 35 (4)https://doi.org/10.1002/adma.202203433
  59. Christopher D. Reinkemeier, Edward A. Lemke. Synthetic Organelles for Multiple mRNA Selective Genetic Code Expansions in Eukaryotes. 2023, 341-369. https://doi.org/10.1007/978-1-0716-2663-4_17
  60. Alexander P. Demchenko. Imaging and Sensing Inside the Living Cells. From Seeing to Believing. 2023, 529-596. https://doi.org/10.1007/978-3-031-19089-6_15
  61. David E. Wright, Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue. Delivery of the selenoprotein thioredoxin reductase 1 to mammalian cells. Frontiers in Molecular Biosciences 2022, 9 https://doi.org/10.3389/fmolb.2022.1031756
  62. Qiang Xiao, Zachary B. Jones, Samantha C. Hatfield, Dallin S. Ashton, Nicholas A. Dalley, Cody D. Dyer, Judah L. Evangelista, Joshua L. Price. Structural guidelines for stabilization of α-helical coiled coils via PEG stapling. RSC Chemical Biology 2022, 3 (9) , 1096-1104. https://doi.org/10.1039/D1CB00237F
  63. Zalina T. Gugkaeva, Maria V. Panova, Alexander F. Smol'yakov, Michael G. Medvedev, Alan T. Tsaloev, Ivan A. Godovikov, Victor I. Maleev, Vladimir A. Larionov. Asymmetric Metal‐Templated Route to Amino Acids with 3‐Spiropyrrolidine Oxindole Core via a 1,3‐Dipolar Addition of Azomethine Ylides to a Chiral Dehydroalanine Ni(II) Complex. Advanced Synthesis & Catalysis 2022, 364 (14) , 2395-2402. https://doi.org/10.1002/adsc.202200446
  64. Sidney M. Hecht. Expansion of the Genetic Code Through the Use of Modified Bacterial Ribosomes. Journal of Molecular Biology 2022, 434 (8) , 167211. https://doi.org/10.1016/j.jmb.2021.167211
  65. Yunhui Xing, Barbie Varghese, Zihan Ling, Ananya Sushanta Kar, Emily Reinoso Jacome, Xi Ren. Extracellular Matrix by Design: Native Biomaterial Fabrication and Functionalization to Boost Tissue Regeneration. Regenerative Engineering and Translational Medicine 2022, 8 (1) , 55-74. https://doi.org/10.1007/s40883-021-00210-5
  66. Wil Biddle, David G. Schwark, Margaret A. Schmitt, John D. Fisk. Directed Evolution Pipeline for the Improvement of Orthogonal Translation Machinery for Genetic Code Expansion at Sense Codons. Frontiers in Chemistry 2022, 10 https://doi.org/10.3389/fchem.2022.815788
  67. Karolina Haernvall, Patrik Fladischer, Heidemarie Schoeffmann, Sabine Zitzenbacher, Tea Pavkov-Keller, Karl Gruber, Michael Schick, Motonori Yamamoto, Andreas Kuenkel, Doris Ribitsch, Georg M. Guebitz, Birgit Wiltschi. Residue-Specific Incorporation of the Non-Canonical Amino Acid Norleucine Improves Lipase Activity on Synthetic Polyesters. Frontiers in Bioengineering and Biotechnology 2022, 10 https://doi.org/10.3389/fbioe.2022.769830
  68. Julien Tailhades. Arylglycine: A Focus on Amino Acid Preparation and Peptide Synthesis. International Journal of Peptide Research and Therapeutics 2022, 28 (1)https://doi.org/10.1007/s10989-021-10308-7
  69. Pritam Giri, Amol D. Pagar, Mahesh D. Patil, Hyungdon Yun. Chemical modification of enzymes to improve biocatalytic performance. Biotechnology Advances 2021, 53 , 107868. https://doi.org/10.1016/j.biotechadv.2021.107868
  70. Dana E. Michels, Brett Lomenick, Tsui-Fen Chou, Michael J. Sweredoski, Alexis Pasulka, . Amino Acid Analog Induces Stress Response in Marine Synechococcus. Applied and Environmental Microbiology 2021, 87 (15)https://doi.org/10.1128/AEM.00200-21
  71. Chao Zhang, Poulami Talukder, Larisa M. Dedkova, Sidney M. Hecht. Facilitated synthesis of proteins containing modified dipeptides. Bioorganic & Medicinal Chemistry 2021, 41 , 116210. https://doi.org/10.1016/j.bmc.2021.116210
  72. Zalina T. Gugkaeva, Alexander F. Smol'yakov, Victor I. Maleev, Vladimir A. Larionov. A general asymmetric synthesis of artificial aliphatic and perfluoroalkylated α-amino acids by Luche's cross-electrophile coupling reaction. Organic & Biomolecular Chemistry 2021, 19 (24) , 5327-5332. https://doi.org/10.1039/D1OB00805F
  73. Ernest G. Nolen, Yuqi M. Cao, Brynn D. Lewis, Madison H. Powers, Andrew W. Thompson, John M. Bennett. Stereoselective Synthesis of (4S,5S)-5-Vinyloxazolidin-2-one-4-carboxylate as a β-Vinylserine Synthetic Equivalent by Vinyl Grignard Addition to an N-Tosyl Version of Garner’s Aldehyde. Synlett 2021, 32 (06) , 601-604. https://doi.org/10.1055/a-1308-0370
  74. Dillon T. Flood, Jordi C. J. Hintzen, Kyle W. Knouse, David E. Hill, Chenxi Lu, Philip A. Cistrone, Jason S. Chen, Takanori Otomo, Philip. E. Dawson. Selenomethionine as an expressible handle for bioconjugations. Proceedings of the National Academy of Sciences 2021, 118 (8)https://doi.org/10.1073/pnas.2005164118
  75. Song Liu, Han Su, Lingli Bu, Jiangyu Yan, Guorui Li, Jing Huang. Fluorogenic probes for mitochondria and lysosomes via intramolecular photoclick reaction. The Analyst 2021, 146 (4) , 1369-1375. https://doi.org/10.1039/D0AN01982H
  76. Mike L.W.J. Smeenk, Jordi Agramunt, Kimberly M. Bonger. Recent developments in bioorthogonal chemistry and the orthogonality within. Current Opinion in Chemical Biology 2021, 60 , 79-88. https://doi.org/10.1016/j.cbpa.2020.09.002
  77. David G. Schwark, Margaret A. Schmitt, John D. Fisk. Directed Evolution of the Methanosarcina barkeri Pyrrolysyl tRNA/aminoacyl tRNA Synthetase Pair for Rapid Evaluation of Sense Codon Reassignment Potential. International Journal of Molecular Sciences 2021, 22 (2) , 895. https://doi.org/10.3390/ijms22020895
  78. Vladimir A. Larionov, Nadezhda V. Stoletova, Victor I. Maleev. Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry. Advanced Synthesis & Catalysis 2020, 362 (20) , 4325-4367. https://doi.org/10.1002/adsc.202000753
  79. Christelle F. Ancajas, Tanei J. Ricks, Michael D. Best. Metabolic labeling of glycerophospholipids via clickable analogs derivatized at the lipid headgroup. Chemistry and Physics of Lipids 2020, 232 , 104971. https://doi.org/10.1016/j.chemphyslip.2020.104971
  80. David G. Schwark, Margaret A. Schmitt, Wil Biddle, John D. Fisk. The Influence of Competing tRNA Abundance on Translation: Quantifying the Efficiency of Sense Codon Reassignment at Rarely Used Codons. ChemBioChem 2020, 21 (16) , 2274-2286. https://doi.org/10.1002/cbic.202000052
  81. Roland Hatzenpichler, Viola Krukenberg, Rachel L. Spietz, Zackary J. Jay. Next-generation physiology approaches to study microbiome function at single cell level. Nature Reviews Microbiology 2020, 18 (4) , 241-256. https://doi.org/10.1038/s41579-020-0323-1
  82. Zhongqiang Wang, Hayden Matthews. Translational incorporation of modified phenylalanines and tyrosines during cell-free protein synthesis. RSC Advances 2020, 10 (19) , 11013-11023. https://doi.org/10.1039/D0RA00655F
  83. Potts K. A., Stieglitz J. T., Lei M., Van Deventer J. A.. Reporter system architecture affects measurements of noncanonical amino acid incorporation efficiency and fidelity. Molecular Systems Design & Engineering 2020, 5 (2) , 573-588. https://doi.org/10.1039/C9ME00107G
  84. . Fluorescence microscopy methods for the study of protein oligomerization. 2020, 1-41. https://doi.org/10.1016/bs.pmbts.2019.12.001
  85. Jared A. Shadish, Cole A. DeForest. Site-Selective Protein Modification: From Functionalized Proteins to Functional Biomaterials. Matter 2020, 2 (1) , 50-77. https://doi.org/10.1016/j.matt.2019.11.011
  86. Aya M. Saleh, Kristen M. Wilding, Sarah Calve, Bradley C. Bundy, Tamara L. Kinzer-Ursem. Non-canonical amino acid labeling in proteomics and biotechnology. Journal of Biological Engineering 2019, 13 (1)https://doi.org/10.1186/s13036-019-0166-3
  87. Yao Wang, Priya Katyal, Jin Kim Montclare. Protein‐Engineered Functional Materials. Advanced Healthcare Materials 2019, 8 (11)https://doi.org/10.1002/adhm.201801374
  88. Katherine Boknevitz, James S. Italia, Bo Li, Abhishek Chatterjee, Shih-Yuan Liu. Synthesis and characterization of an unnatural boron and nitrogen-containing tryptophan analogue and its incorporation into proteins. Chemical Science 2019, 10 (19) , 4994-4998. https://doi.org/10.1039/C8SC05167D
  89. Xuexia Li, Qiang Zhu, Xiaoliu Shi, Yaxian Cheng, Xueliu Li, Huan Xu, Xiaotao Duan, Linda C. Hsieh-Wilson, Jennifer Chu, Jerry Pelletier, Maowei Ni, Zhiguo Zheng, Sihui Li, Wen Yi. O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis. Proceedings of the National Academy of Sciences 2019, 116 (16) , 7857-7866. https://doi.org/10.1073/pnas.1813026116
  90. Vladimir A. Larionov, Nadezhda V. Stoletova, Vladislav I. Kovalev, Alexander F. Smol'yakov, Tat'yana F. Savel'yeva, Victor I. Maleev. A general synthesis of unnatural α-amino acids by iron-catalysed olefin–olefin coupling via generated radicals. Organic Chemistry Frontiers 2019, 6 (8) , 1094-1099. https://doi.org/10.1039/C9QO00108E
  91. Tonima Nandy, Saptarsi Mondal, Prashant Chandra Singh. Solvent organization around the noncanonical part of tyrosine modulates its fluorescence properties. Physical Chemistry Chemical Physics 2019, 21 (11) , 6042-6050. https://doi.org/10.1039/C8CP06410E
  92. Vincenzo De Filippis, Nicola Pozzi, Laura Acquasaliente, Ilaria Artusi, Giulia Pontarollo, Daniele Peterle. Protein engineering by chemical methods: Incorporation of nonnatural amino acids as a tool for studying protein folding, stability, and function. Peptide Science 2018, 110 (5)https://doi.org/10.1002/pep2.24090
  93. Lingyan Shi, Yihui Shen, Wei Min. Invited Article: Visualizing protein synthesis in mice with in vivo labeling of deuterated amino acids using vibrational imaging. APL Photonics 2018, 3 (9)https://doi.org/10.1063/1.5028134
  94. Zhongwei Xue, Enkang Zhang, Jian Liu, Jiahuai Han, Shoufa Han. Bioorthogonal Conjugation Directed by a Sugar‐Sorting Pathway for Continual Tracking of Stressed Organelles. Angewandte Chemie 2018, 130 (32) , 10253-10258. https://doi.org/10.1002/ange.201802972
  95. Zhongwei Xue, Enkang Zhang, Jian Liu, Jiahuai Han, Shoufa Han. Bioorthogonal Conjugation Directed by a Sugar‐Sorting Pathway for Continual Tracking of Stressed Organelles. Angewandte Chemie International Edition 2018, 57 (32) , 10096-10101. https://doi.org/10.1002/anie.201802972
  96. Xiao‐Wei Wang, Dong Liu, Guang‐Zhong Yin, Wen‐Bin Zhang. Tuning Mechanical Properties of Protein Hydrogels. 2018, 295-309. https://doi.org/10.1002/9781119390350.ch15
  97. Vladimir A. Larionov, Hovhannes V. Adonts, Zalina T. Gugkaeva, Alexander F. Smol'yakov, Ashot S. Saghyan, Mansur S. Miftakhov, Svetlana A. Kuznetsova, Victor I. Maleev, Yuri N. Belokon. The Elaboration of a General Approach to the Asymmetric Synthesis of 1,4‐Substituted 1,2,3‐Triazole Containing Amino Acids via Ni(II) Complexes. ChemistrySelect 2018, 3 (11) , 3107-3110. https://doi.org/10.1002/slct.201800228
  98. Han-Hsuan Liu, Daniel B McClatchy, Lucio Schiapparelli, Wanhua Shen, John R Yates, Hollis T Cline. Role of the visual experience-dependent nascent proteome in neuronal plasticity. eLife 2018, 7 https://doi.org/10.7554/eLife.33420
  99. Jean‐François Lutz. Defining the Field of Sequence‐Controlled Polymers. 2018, 1-26. https://doi.org/10.1002/9783527806096.ch1
  100. Mark B. van Eldijk, Jan C. M. van Hest. Residue-Specific Incorporation of Noncanonical Amino Acids for Protein Engineering. 2018, 137-145. https://doi.org/10.1007/978-1-4939-7574-7_8

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