Communication

Iterative In Situ Click Chemistry Creates Antibody-like Protein-Capture Agents†

  1. Heather D. Agnew1,
  2. Rosemary D. Rohde1,
  3. Steven W. Millward Dr.1,
  4. Arundhati Nag1,
  5. Woon-Seok Yeo Dr.1,3,
  6. Jason E. Hein Dr.2,
  7. Suresh M. Pitram Dr.2,
  8. Abdul Ahad Tariq1,
  9. Vanessa M. Burns1,
  10. Russell J. Krom1,
  11. Valery V. Fokin Prof.2,
  12. K. Barry Sharpless Prof. 2,
  13. James R. Heath Prof.1

Article first published online: 19 MAR 2009

DOI: 10.1002/anie.200900488

Issue

Angewandte Chemie International Edition

Angewandte Chemie International Edition

Volume 48, Issue 27, pages 4944–4948, June 22, 2009

Additional Information

How to Cite

Agnew, Heather D., Rohde, Rosemary D., Millward, Steven W., Nag, A., Yeo, W.-S., Hein, Jason E., Pitram, Suresh M., Tariq, A., Burns, Vanessa M., Krom, Russell J., Fokin, Valery V., Sharpless, K. Barry. and Heath, James R. (2009), Iterative In Situ Click Chemistry Creates Antibody-like Protein-Capture Agents. Angew. Chem. Int. Ed., 48: 4944–4948. doi: 10.1002/anie.200900488

Author Information

  1. 1

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-2355 http://www.its.caltech.edu/∼heathgrp

  2. 2

    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)

  3. 3

    Current address: Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701 (Korea)

  1. †

    This research was supported by the National Cancer Institute, grant No. 5U54 CA119347 (J.R.H.), the W. M. Keck Foundation (K.B.S.), and a subcontract from the MITRE Corporation (J.R.H.). Postdoctoral and graduate fellowships were provided by the NSF and PEO (H.D.A.), the Gates Foundation (R.D.R.), the NSERC (J.E.H.), and the NCI (S.W.M.). We also acknowledge H. C. Kolb, S. S. Lee, J. Cha, J. Lim, S. Tan, S. Y. Yeo, A. Srivastava, M. Barrientos, E. Johnson Chavarria, A. Stuparu, J. Vielmetter, and C. S. Parker for useful discussions and assistance.

Publication History

  1. Issue published online: 17 JUN 2009
  2. Article first published online: 19 MAR 2009
  3. Manuscript Received: 26 JAN 2009

Funded by

  • National Cancer Institute. Grant Number: 5U54 CA119347
  • W. M. Keck Foundation
  • MITRE Corporation

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Keywords:

  • click chemistry;
  • combinatorial chemistry;
  • inhibitors;
  • peptides;
  • protein-capture agents

Abstract

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Special agents for protein capture: Iterative in situ click chemistry (see scheme for the tertiary ligand screen) and the one-bead–one-compound method for the creation of a peptide library enable the fragment-based assembly of selective high-affinity protein-capture agents. The resulting ligands are water-soluble and stable chemically, biochemically, and thermally. They can be produced in gram quantities through copper(I)-catalyzed cycloaddition.

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