Carbon Suboxide and Proteins

In Paper I of this series (1) there was reported the reaction of carbon suboxide, C302, with an aqueous solution of glycine to give malonyldiglycine.The present communication describes further studies of the behavior of this reagent with amino acids in the presence of water.Like glycine, lysine adds to C302 through its a-amino group if the e-amino is protected.Thus there was obtained from c-benzoyldl-lysine the expected malonyldi-(E-benzoyl-dl-lysine)cu-amide.This behavior can be accepted as typical of all primary a-amino groups, and indicates that the free terminal amino groups in proteins react similarly.The e-amino group of lysine also gives well defined crystalline products if the a! group is protected.From or-benzoyl-Z-lysine there was obtained malonyldi-(a-benzoyl-Z-lysine)e-amide, which formed equally well in solutions of pH 8.0 or 6.0.The loss of amino nitrogen by proteins on exposure to GO2 has already been attributed to the reaction of this group in the lysine residue.There is, however, in malonyl proteins more combined malonic acid than can be accounted for by amide formation alone (1).This led to the investigation of the behavior of C&O2 with suitable derivatives of tyrosine, an amino acid which is known to be acetylated at its phenolic hydroxyl by ketene (2).Both the diester, di-(N-carbobenzoxy-I-tyrosyl) malonate and the monoester, mono-(N-carbobenzoxy-Z-tyrosyl) malonate were found to be present after the addition of 1.5 molar equivalents of C302 to a slightly alkaline solution of carbobenzoxytyrosine.The yields,