Leader Peptide‐Free In Vitro Reconstitution of Microviridin Biosynthesis Enables Design of Synthetic Protease‐Targeted Libraries

Microviridins are a family of ribosomally synthesized and post‐translationally modified peptides with a highly unusual architecture featuring non‐canonical lactone as well as lactam rings. Individual variants specifically inhibit different types of serine proteases. Here we have established an efficient in vitro reconstitution approach based on two ATP‐grasp ligases that were constitutively activated using covalently attached leader peptides and a GNAT‐type N‐acetyltransferase. The method facilitates the efficient in vitro one‐pot transformation of microviridin core peptides to mature microviridins. The engineering potential of the chemo‐enzymatic technology was demonstrated for two synthetic peptide libraries that were used to screen and optimize microviridin variants targeting the serine proteases trypsin and subtilisin. Successive analysis of intermediates revealed distinct structure–activity relationships for respective target proteases.     

Scandium as an Element Intermediate between Rare Earth and Transition Metals in Intermetallics: Crystal Structures of Sc2Fe12P7, Sc3.6Fe10.4P7, and Sc2Co4P3. Other New Compounds with Zr2Fe12P7, Hf2Co4P3, Sc5Co19P12, and Yb6Co30P19 Type Structures

Abstract. Twenty five ternary phosphides crystallizing with four different but closely related structure types were prepared using elemental tin as a flux. Their lattice constants are reported. New compounds include Sc₂Fe₁₂P₇, Sc_3.6Fe_10.4P₇, Y₂Co₁₂P₇, and Hf₂T₁₂P₇ with T = Fe, Co, Ni. They crystallize with the hexagonal Zr₂Fe₁₂P₇ type structure, which was refined from single‐crystal X‐ray data of Sc_3.6Fe_10.4P₇: a = 944.1(1) pm, c = 363.4(1) pm, R = 0.041 for 719 unique structure factors and 23 variable parameters. The excess scandium atoms occupy one of the four iron sites of the Zr₂Fe₁₂P₇ type structure which has a higher coordination number than the other three iron sites. The two isotypic phosphides Sc₂Fe₁₂P₇ and Sc_3.6Fe_10.4P₇ do not form a continuous series of solid solutions. The new compounds Sc₂Co₄P₃ and Sc₂Ni₄P₃ are isotypic with Hf₂Co₄P₃. This hexagonal structure was refined for Sc₂Co₄P₃ from single crystal data: a = 1211.5(2) pm, c = 363.7(1) pm, R = 0.025 for 500 F_o and 38 variables. Other new compounds reported are Sc₅Ni₁₉P₁₂, Zr₅Fe₁₉P₁₂, Hf₅Fe₁₉P₁₂, and Hf₅Co₁₉P₁₂ which crystallize with Sc₅Co₁₉P₁₂ type structure, and the Yb₆Co₃₀P₁₉ type phosphides Sc₆Co₃₀P₁₉, Zr₆Co₃₀P₁₉, and Hf₆Co₃₀P₁₉. The structural relationships of these ternary phosphides are discussed with special attention to the environments of the transition metal atoms.     

Synthesis of a GaN Cage Compound with a Hydrazinetetraide Fragment, [N?N]4−, Stabilised by Six Gallium Atoms

Thermolysis of the bicyclic gallium hydrazide [(GaMe₂)₄(NH? NMe)(NH? NHMe)₂] ( 1 ) yielded the unique cage compound [(GaMe)₄(GaMe₂)₄(N₂)(NH? NMe)₄] ( 2 ). Compound 2 contains a remarkable hydrazinetetraide moiety, [N? N]^4?, as the central structural motif which is stabilised by coordination to six gallium atoms.     

A Simple Preparation of Dialkylsulfinyl- and Dialkylsulfonyl-Sulfides

A first general approach to sulfinyl-sulfides R¹-S(O)-(CH₂)_n-S-R² and sulfonyl-sulfides R¹-S(O₂)-(CH₂)_n-S-R² with variable and different alkyl substituents is described.