Synlett
DOI: 10.1055/a-2214-7612
synpacts
Thieme Chemistry Journals Awardees 2023

The Cyanopyridine–Aminothiol Click Reaction: Expanding Horizons in Chemical Biology

Christoph Nitsche  ∗
C.N. thanks the Australian Research Council for a Future Fellowship (FT220100010).
› Further Information
    Permissions and Reprints All articles of this category


Abstract

Bioorthogonal reactions hold significant promise for applications in chemical biology. Despite their potential, nitriles have often been overlooked as reactive functional groups for selective bioconjugation. The condensation reaction between cyanopyridines and 1,2-aminothiols stands out as a particularly favorable nitrile modification strategy that proceeds under biocompatible conditions. Cyanopyridines can be seamlessly incorporated into peptides and proteins through both chemical and biotechnological approaches. Similarly, the selective integration of 1,2-aminothiols into peptides and proteins is achievable, leveraging the uniquely reactive N-terminal cysteine functional group.

1 Introduction

2 The Biocompatible Condensation Reaction

3 Peptide Macrocyclisation

4 Orthogonality to Cysteine

5 Combination with Genetic Encoding

6 Conclusion

Key words

click chemistry - bioconjugation - peptides - proteins - bioorthogonal - nitrile - cysteine


Publication History

Received: 09 November 2023

Accepted after revision: 20 November 2023

Accepted Manuscript online:
20 November 2023

Article published online:
15 January 2024

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

    • 1a Zaia J. Anal. Bioanal. Chem. 2023; 415: 527
      CrossrefPubMed
    • 1b Sletten EM, Bertozzi CR. Angew. Chem. Int. Ed. 2009; 48: 6974
      CrossrefPubMed
    • 1c Bird RE, Lemmel SA, Yu X, Zhou QA. Bioconjugate Chem. 2021; 32: 2457
      CrossrefPubMed
    • 1d Scinto SL, Bilodeau DA, Hincapie R, Lee W, Nguyen SS, Xu M, am Ende CW, Finn MG, Lang K, Lin Q, Pezacki JP, Prescher JA, Robillard MS, Fox JM. Nat. Rev. Methods Primers 2021; 1: 30
      CrossrefPubMed
    • 2a Agard NJ, Prescher JA, Bertozzi CR. J. Am. Chem. Soc. 2004; 126: 15046
      CrossrefPubMed
    • 2b Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
      CrossrefPubMed
    • 2c Tornøe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
      CrossrefPubMed
  • 4 Maguire OR, Zhu J, Brittain WD. G, Hudson AS, Cobb SL, O’Donoghue AC. Chem. Commun. 2020; 56: 6114
    CrossrefPubMed
    • 5a Berteotti A, Vacondio F, Lodola A, Bassi M, Silva C, Mor M, Cavalli A. ACS Med. Chem. Lett. 2014; 5: 501
      CrossrefPubMed
    • 5b Maltsev OV, Walter V, Brandl MJ, Hintermann L. Synthesis 2013; 45: 2763
      Article in Thieme Connect
    • 5c Oballa RM, Truchon J.-F, Bayly CI, Chauret N, Day S, Crane S, Berthelette C. Bioorg. Med. Chem. Lett. 2007; 17: 998
      CrossrefPubMed
    • 5d Toyama T, Saitoh T, Takahashi Y, Oka K, Citterio D, Suzuki K, Nishiyama S. Chem. Lett. 2017; 46: 753
      Crossref
  • 6 Tamura T, Inoue M, Yoshimitsu Y, Hashimoto I, Ohashi N, Tsumura K, Suzuki K, Watanabe T, Hohsaka T. Bull. Chem. Soc. Jpn. 2022; 95: 359
    Crossref
    • 7a Ren H, Xiao F, Zhan K, Kim Y.-P, Xie H, Xia Z, Rao J. Angew. Chem. Int. Ed. 2009; 48: 9658
      CrossrefPubMed
    • 7b Proj M, Strašek N, Pajk S, Knez D, Sosič I. Bioconjugate Chem. 2023; 34: 1271
      CrossrefPubMed
  • 8 Ramil CP, An P, Yu Z, Lin Q. J. Am. Chem. Soc. 2016; 138: 5499
    CrossrefPubMed
  • 9 Liu M, Yoshisada R, Amedi A, Hopstaken AJ. P, Pascha MN, de Haan CA. M, Geerke DP, Poole DA. III, Jongkees SA. K. Chem. Eur. J. 2023; 29: e202203923
    CrossrefPubMed
  • 10 Nitsche C, Onagi H, Quek J.-P, Otting G, Luo D, Huber T. Org. Lett. 2019; 21: 4709
    CrossrefPubMed
  • 11 Patil NA, Quek J.-P, Schroeder B, Morewood R, Rademann J, Luo D, Nitsche C. ACS Med. Chem. Lett. 2021; 12: 732
    CrossrefPubMed
  • 12 Ullrich S, George J, Coram A, Morewood R, Nitsche C. Angew. Chem. Int. Ed. 2022; 61: e202208400
    CrossrefPubMed
  • 13 Morewood R, Nitsche C. Chem. Sci. 2021; 12: 669
    CrossrefPubMed
  • 14 Coram AE, Morewood R, Voss S, Price JL, Nitsche C. J. Pept. Sci. 2024; 30: e3551
    PubMed
  • 15 Ullrich S, Sasi VM, Mahawaththa MC, Ekanayake KB, Morewood R, George J, Shuttleworth L, Zhang X, Whitefield C, Otting G, Jackson C, Nitsche C. Bioorg. Med. Chem. Lett. 2021; 50: 128333
    CrossrefPubMed
  • 16 Liu M, Morewood R, Yoshisada R, Pascha MN, Hopstaken AJ. P, Tarcoveanu E, Poole DA, de Haan CA. M, Nitsche C, Jongkees SA. K. Chem. Sci. 2023; 14: 10561
    CrossrefPubMed
  • 17 Iskandar SE, Pelton JM, Wick ET, Bolhuis DL, Baldwin AS, Emanuele MJ, Brown NG, Bowers AA. J. Am. Chem. Soc. 2023; 145: 1512
    CrossrefPubMed
  • 18 Fan L, Yu Y, Jayne C, Frost JR, Scott JD. Org. Lett. 2023; 25: 8038
    CrossrefPubMed
  • 19 Shi Y, Wu Y.-r, Yu J.-q, Zhang W.-n, Zhuang C.-l. RSC Adv. 2021; 11: 2359
    CrossrefPubMed
  • 20 Abdelkader EH, Qianzhu H, George J, Frkic RL, Jackson CJ, Nitsche C, Otting G, Huber T. Angew. Chem. Int. Ed. 2022; 61: e202114154
    CrossrefPubMed
  • 21 Nguyen DP, Elliott T, Holt M, Muir TW, Chin JW. J. Am. Chem. Soc. 2011; 133: 11418
    CrossrefPubMed