Design, Synthesis, and Evaluation of Gluten Peptide Analogs as Selective Inhibitors of Human Tissue Transglutaminase Felix Hausch, Tuula Halttunen, Markku.

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Design, Synthesis, and Evaluation of Gluten Peptide Analogs as Selective Inhibitors of Human Tissue Transglutaminase Felix Hausch, Tuula Halttunen, Markku Mäki, Chaitan Khosla Chemistry & Biology Volume 10, Issue 3, Pages 225-231 (March 2003) DOI: 10.1016/S1074-5521(03)00045-0

Figure 1 Reactive Glutamine Isosteres and Their Gluten Peptide Analogs Three different reactive isoteres of glutamine were evaluated as potential inhibitors of human tissue transglutaminase. The reactive moieties are shaded. Chemistry & Biology 2003 10, 225-231DOI: (10.1016/S1074-5521(03)00045-0)

Figure 2 Synthesis of Protected or Peptide-Bound Reactive Glutamine Isosteres For details, see Experimental Procedures. Chemistry & Biology 2003 10, 225-231DOI: (10.1016/S1074-5521(03)00045-0)

Figure 3 Irreversible Inhibition of Tissue Transglutaminase by 6-Diazo-5-Oxo-Norleucine-Containing Compounds (A) Progress curve analysis of tissue transglutaminase incubated with 1 μM Ac-PQP-DON-LPF-NH2 4c and 45 mM (closed squares), 60 mM (closed triangles), 90 mM (open circles), or 120 mM (closed circles) of the substrate Cbz-Gln-Gly. Incubation with 45 mM Cbz-Gln-Gly alone without inhibitor (open squares). Inset: progress curves were nonlinear least-squares fitted, as described in the Experimental Procedures section, to calculate the inhibition constants. (B) Double-reciprocal plot of competitive inhibition of tissue transglutaminase by Cbz-DON-OMe 4b. Initial velocities (v0) of Cbz-Gln-Gly deamidation in the presence of the indicated amounts of this inhibitor were obtained by nonlinear least-squares fitting of the corresponding progress curves. Chemistry & Biology 2003 10, 225-231DOI: (10.1016/S1074-5521(03)00045-0)

Figure 4 Inhibition of T84 Human Intestinal Epithelial Cell Differentiation Inhibition of T84 differentiation was performed on cells from 11 days cultures and is expressed as percent differentiated T84 cell colonies relative to an equivalent DMSO control. The columns represent the average of three independent sets of experiments with two replicates, and the bars represent the standard deviations. Chemistry & Biology 2003 10, 225-231DOI: (10.1016/S1074-5521(03)00045-0)