Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Drug discovery

Tools and rules for macrocycles

The application of macrocycles to previously undruggable targets has aroused a great deal of interest in this structural class. Recent studies advance our understanding of the way macrocycles bind protein targets and provide new strategies and tools to generate peptide-based macrocycles.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Development of macrocycle drugs.
Figure 2: Cyclization of peptides with butelase 1.


  1. Driggers, E.M., Hale, S.P., Lee, J. & Terrett, N.K. Nat. Rev. Drug Discov. 7, 608–624 (2008).

    Article  CAS  Google Scholar 

  2. Villar, E.A. et al. Nat. Chem. Biol. 10.1038/nchembio.1584 (20 July 2014).

  3. Gavenonis, J., Sheneman, B.A., Siegert, T.R., Eshelman, M.R., Kritzer, J.A. Nat. Chem. Biol. 10.1038/nchembio.1580 (20 July 2014).

    Google Scholar 

  4. Nguyen, G.K.T. et al. Nat. Chem. Biol. 10.1038/nchembio.1586 (20 July 2014).

  5. Giordanetto, F. & Kihlberg, J.J. Med. Chem. 57, 278–295 (2014).

    Article  CAS  Google Scholar 

  6. Higueruelo, A.P., Jubb, H. & Blundell, T.L. Curr. Opin. Pharmacol. 13, 791–796 (2013).

    Article  CAS  Google Scholar 

  7. Robinson, J.A., Demarco, S., Gombert, F., Moehle, K. & Obrecht, D. Drug Discov. Today 13, 944–951 (2008).

    Article  CAS  Google Scholar 

  8. White, C.J. & Yudin, A.K. Nat. Chem. 3, 509–524 (2011).

    Article  CAS  Google Scholar 

  9. Hipolito, C.J. & Suga, H. Curr. Opin. Chem. Biol. 16, 196–203 (2012).

    Article  CAS  Google Scholar 

  10. Heinis, C., Rutherford, T., Freund, S. & Winter, G. Nat. Chem. Biol. 5, 502–507 (2009).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Christian Heinis.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heinis, C. Tools and rules for macrocycles. Nat Chem Biol 10, 696–698 (2014).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research