Anchoring ligand-bound transition metals to proteins covalently or noncovalently provides conjugates that are of potential interest as enantioselective hybrid catalysts in organic synthesis. [1] Although a number of studies regarding this concept have appeared, examples of truly high enantioselectivity (> 90 % ee) are rare. Indeed, pronounced degrees of asymmetric induction cannot be expected just because the protein environment is chiral. Herein we report Cu II -catalyzed Diels-Alder reactions of azachalcones 1 a-e with cyclopentadiene (2) in an aqueous medium in the presence of appropriate proteins, leading to products 3 [Eq. ( 1)] with surprisingly high enantiopurities (85-98 % ee). The first transition-metal-catalyzed asymmetric Diels-Alder reactions in water were reported by Engberts and co-workers, who performed the cycloaddition of 1 a with 2 in the presence of water-soluble Cu II complexes of chiral a-amino acids (up to 74 % ee of the major endo product 3 a). [2] More recently Roelfs and Feringa carried out the same reaction also in water with Cu II conjugates of DNA, resulting in a maximum of 53 % ee for endo-3 a (endo/exo 91:9). [3] Moreover, endo/exo selectivity of certain Diels-Alder reactions is known to be influenced by the presence of Bakers yeast, [4] and in another study Colonna et al. showed that enantioselectivity up to 38 % ee can be achieved upon adding bovine serum albumin