Solution-Phase Synthesis of the Fluorogenic TGase 2 Acyl Donor Z-Glu(HMC)-Gly-OH and its Use for Inhibitor and Amine Substrate Characterisation
Solution-Phase Synthesis of the Fluorogenic TGase 2 Acyl Donor Z-Glu(HMC)-Gly-OH and its Use for Inhibitor and Amine Substrate Characterisation
Wodtke, R.; Pietsch, M.; Löser, R.
A reliable solution-phase synthesis of the water-soluble dipeptidic fluorogenic transglutaminase substrate Z-Glu(HMC)-Gly-OH is presented. The route started from Z-Glu-OH, which was converted into the corresponding cyclic anhydride. This building block was transformed into the regioisomeric - and -dipeptides. Key step was the esterification of Z-Glu-Gly-OtBu with 4-methylumbelliferone. The final substrate compound was obtained in an acceptable yield and excellent purity without the need of purification by RP-HPLC. The advantage of this acyl donor substrate for the kinetic characterisation of inhibitors and amine-type acyl acceptor substrates is demonstrated by evaluating commercially available or literature-known irreversible inhibitors and the biogenic amines serotonin, histamine and dopamine, respectively.
Keywords: fluorogenic enzyme substrates; side-chain esterified peptides; aryl esters; peptide synthesis; enzyme kinetics; biogenic amines
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Analytical Biochemistry 595(2020), 113612
DOI: 10.1016/j.ab.2020.113612
Cited 4 times in Scopus
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