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Preparation of the functionalizable methionine surrogate azidohomoalanine via copper-catalyzed diazo transfer

Nature Protocols volume 2, pages 1879–1883 (2007)Cite this article

Abstract

The azide functional group has assumed a prominent role in chemical biology efforts in recent years. Azides may be readily introduced into proteins upon replacement of methionine residues with the non-canonical amino acid azidohomoalanine (AHA). This protocol describes a synthetic route to AHA based on the copper-catalyzed conversion of amines to azides. An alternate protocol for the preparation of AHA is presented in a companion paper. The synthesis and purification of AHA via the route described herein can be completed in 3–4 days.

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Figure 1: Routes to covalent functionalization of azides.
Figure 2
Figure 3: Schematic of synthesis of AHA from protected diaminobutyric acid.

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Acknowledgements

We thank Rebecca Connor and Nick Fisk for refinements to this protocol. This work was supported by NIH, by an NSF graduate fellowship to A.J.L. and by a grant from the Netherlands Organization for Scientific Research to M.K.S.V.

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  1. A James Link & Mandy K S Vink

    Present address: Present address: Department of Chemical Engineering, Princeton University, A207 Engineering Quadrangle, Princeton, New Jersey 08544, USA (A.J.L.). BioCatalytics Europe GmbH, Parkring 18, A-8074, Grambach, Austria (M.K.S.V.).,

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  1. Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, Pasadena, 91106, California, USA

    A James Link, Mandy K S Vink & David A Tirrell

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  1. Mandy K S Vink
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Correspondence to A James Link.

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Link, A., Vink, M. & Tirrell, D. Preparation of the functionalizable methionine surrogate azidohomoalanine via copper-catalyzed diazo transfer. Nat Protoc 2, 1879–1883 (2007). https://doi.org/10.1038/nprot.2007.268

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