Kofoed Jacob, Darbre Tamis, Reymond Jean-Louis
Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH-3012, Berne, Switzerland.
Org Biomol Chem. 2006 Sep 7;4(17):3268-81. doi: 10.1039/b607342e. Epub 2006 Jul 26.
Peptide dendrimers were investigated as synthetic models for aldolase enzymes. Combinatorial libraries were prepared with aldolase active residues such as lysine and proline placed at the dendrimer core or near the surface. On-bead selection for aldolase activity was carried out using the dye-labelled 1,3-diketone 1a, suitable for covalent trapping of enamine-reactive side-chains, and the fluorogenic enolization probe 6. Aldolase dendrimers catalyzed the aldol reaction of acetone, dihydroxyacetone and cyclohexanone with nitrobenzaldehyde. Much like enzymes, the dendrimers exhibited strong aldolase activity in aqueous medium, but were also active in organic solvent. Dendrimer-catalyzed aldol reactions reached complete conversion in 3 h at 25 degrees C with 1 mol% catalyst and gave aldol products with up to 65% ee. A positive dendritic effect in catalysis was observed with both lysine and proline based aldolase dendrimer catalysts.
肽树枝状大分子作为醛缩酶的合成模型进行了研究。制备了组合文库，将醛缩酶活性残基如赖氨酸和脯氨酸置于树枝状大分子的核心或靠近表面。使用适合对烯胺反应性侧链进行共价捕获的染料标记的1,3 - 二酮1a和荧光烯醇化探针6，对珠子上的醛缩酶活性进行筛选。醛缩酶树枝状大分子催化丙酮、二羟基丙酮和环己酮与硝基苯甲醛的羟醛反应。与酶非常相似，树枝状大分子在水性介质中表现出很强的醛缩酶活性，但在有机溶剂中也有活性。树枝状大分子催化的羟醛反应在25℃下使用1 mol%的催化剂3小时内达到完全转化，并得到ee值高达65%的羟醛产物。基于赖氨酸和脯氨酸的醛缩酶树枝状大分子催化剂在催化中均观察到了正的树枝状效应。
