The ability to rationally modify enzymes to perform novel chemical transformations is essential for the rapid production of next-generation protein therapeutics. Here we describe the use of chemical principles to identify a naturally occurring acid-active peptidase, and the subsequent use of computational protein design tools to reengineer its specificity toward immunogenic elements found in gluten that are the proposed cause of celiac disease. The engineered enzyme exhibits a kcat/KM of 568 M–1 s–1, representing a 116-fold greater proteolytic activity for a model gluten tetrapeptide than the native template enzyme, as well as an over 800-fold switch in substrate specificity toward immunogenic portions of gluten peptides. The computationally engineered enzyme is resistant to proteolysis by digestive proteases and degrades over 95% of an immunogenic peptide implicated in celiac disease in under an hour. Thus, through identification of a natural enzyme with the pre-existing qualities relevant to an ultimate goal and redefinition of its substrate specificity using computational modeling, we were able to generate an enzyme with potential as a therapeutic for celiac disease.

Lanthanum fluoride selenides (A-LaFSe, B-LaFSe and La2F4Se) have been synthesized through high-temperature experiments from an appropriate La/LaF3/Se mixture and characterized using single-crystal as well as powder X-ray diffractometry and UV/Vis diffuse reflectance spectroscopy. A-type LaFSe crystallizes in the tetragonal space group P4/nmm with a = 413.79(3) pm, c = 715.24(5) pm, and Z = 2 with the PbFCl-type structure; B-type LaFSe in the hexagonal space group P63/mmc with a = 421.602(2) pm, c = 818.163(7) pm, and Z = 2 with the CeHSe-type structure; and La2F4Se in the trigonal space group R3̅m with a = 417.86(2) pm, c = 2326.78(9) pm, and Z = 3 in the Ce2F4Se-type structure, respectively, in agreement with the earlier work. The experiments are complemented by crystal-structure predictions for LaFSe, which were performed using global optimization with empirical potentials and ab initio energy local minimizations. The results of the calculations concur with the experimentally observed structures and predict additional, so far unknown LaFSe polymorphs. The electronic properties were investigated both experimentally and theoretically, demonstrating the possibilities for band gap engineering in LaFSe.

Dark ruby‐red, transparent, triangular plate‐shaped single crystals of Eu2H3Cl and colorless, transparent, needle‐shaped single crystals of Eu7F12Cl2 were obtained by solid‐state reactions of Eu, NaH, NaCl, and Na (2:4:1:2 molar ratio) or Eu, EuCl3, and LiF (1:1:4 molar ratio), respectively, in silica‐jacketed tantalum ampoules at 900 °C for 13 h. Eu2H3Cl crystallizes isotypically to Ba2H3X (X = Cl, Br, I) in the trigonal space group P$\bar{3}$m1 (no. 164) with lattice parameters a = 409.67(4) and c = 696.18(7) pm, whereas Eu7F12Cl2 crystallizes isotypically to Ba7F12Cl2 or Sr7H12Cl2 in the hexagonal space group P$\bar{6}$ (no. 174) with lattice parameters a = 1002.31(5) and c = 392.54(2) pm. Both compounds contain Eu2+ cations with coordination numbers as high as nine (Eu7F12Cl2) and ten (Eu2H3Cl) with respect to the halide anions (F– or H– and Cl–). The structural results are corroborated by EUTAX and MAPLE calculations on both ternary mixed‐anion europium(II) chlorides in comparison to these for related binary and ternary compounds with divalent europium.

The two series of title compounds are prepared from mixtures of MF3 (M: La—Nd, Sm, Gd—Ho), M2O3, M, and Se using excess CsI as a flux (Nb tubes, 850 °C, 10 d).

Two hexagonal series of lanthanoid(III) oxide fluoride selenides with similar structure types can be obtained by the reaction of the components MF 3 , M 2 O 3 , M, and Se in sealed niobium tubes at 850°C using CsI as fluxing agent. The compounds with the lighter and larger representatives (M = La -Nd) occur with the formula M 6 O 2 F 8 Se 3 , whereas with the heavier and smaller ones (M = Nd, Sm, Gd -Ho) their composition is M 2 OF 2 Se. For both systems singlecrystal determinations were used in all cases. The compounds crystallize in the hexagonal crystal system (space group: P6 3 /m) with lattice parameters of a = 1394-1331 pm and c = 403-372 pm (Z = 2 for M 6 O 2 F 8 Se 3 and Z = 6 for M 2 OF 2 Se). The (M1) 3+ cations show dif-* Prof. Dr. Th. Schleid