Fmoc-Aha-OH

Fmoc-Aha-OH
Nα-Fmoc-L-azidohomoalanine (Fmoc-Dab(N3)-OH); (2S)-4-azido-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoic acid

An Fmoc amino acid carrying an azide two methylenes out from the α-carbon; the free amino acid is azidohomoalanine, (2S)-2-amino-4-azidobutanoic acid. The alias Fmoc-Dab(N3)-OH describes the connectivity — 2,4-diaminobutyric acid with the γ-nitrogen replaced by the azide — but nothing on the side chain is protected and no side-chain amine remains: the azide goes into the finished peptide, and the residue couples like any other Fmoc amino acid. The catalogue's other azide, Fmoc-Lys(N3)-OH (41092), is 6-azido-L-norleucine, four methylenes out.

The azide is there to be reacted once the chain is built. In the reported solid-phase work, copper(I) catalysis joined terminal alkynes to primary, secondary and tertiary alkyl azides, aryl azides and an azido sugar, giving 1,4-substituted 1,2,3-triazoles in peptide backbones or side chains with more than 95% conversion and purity in most cases, under conditions reported to be fully compatible with solid-phase peptide synthesis on polar supports. Fmoc-Pra-OH (47252), the propargylglycine in this catalogue, supplies the matching alkyne.

Where copper cannot be used — the Cu(I) catalyst was reported to be toxic to cells — a strained cyclooctyne reacts with an azide under physiological conditions and with no catalyst, in that study modifying biomolecules in vitro and on living cells with no apparent toxicity. In a further report this residue's free amino acid, standing in for methionine in bacterially expressed proteins, let those proteins be selectively modified among other cellular proteins by Staudinger ligation with triarylphosphine reagents.

Applications

• Side-chain azide for copper-catalysed or copper-free cycloaddition after chain assembly
• Site-specific labeling and bioconjugation at one defined residue
• Triazole-linked conjugates built on the resin or after cleavage

Storage
Store frozen, at or below -4 °C, in a tightly closed container, and let it reach room temperature before opening.

References

1. Tornøe CW et al. Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides. The Journal of Organic Chemistry 2002, 67, 3057–3064. doi:10.1021/jo011148j
2. Agard NJ et al. A Strain-Promoted [3 + 2] Azide–Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems. Journal of the American Chemical Society 2004, 126, 15046–15047. doi:10.1021/ja044996f
3. Kiick KL et al. Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation. Proceedings of the National Academy of Sciences 2002, 99, 19–24. doi:10.1073/pnas.012583299

For research use only. Not for human or veterinary use.