Alkylation of a Tripeptide by a Carcinogen: The Crystal Structures of Sarcosylglycylglycine, 9-Methyl-10-chloromethylanthracene, and Their Reaction Product

The effect of alkylation of a peptide by a polycyclic aromatic hydrocarbon has been investigated as a model for protein-carcinogen interactions. The tripeptide sarcosylglycylglycine (I) reacts with 9-methyl-10-chloromethylanthracene (II) with the elimination of HCl to form the alkylated tripeptide (III). The crystal data are (I) a = 20.847 (3), b = 10.252 ( 1 ), and c = 8.719 (1) \, space group Pbca, Z = 8; (II) a = 14.379 (1), b = 16.359 (l), c = 5.0993 (4) \, space group p21 21 21, Z = 4; and (111) a = 19.022 (4), b = 10.727 (2), c = 10.728 (2) \, β = 94.24 (2)°, space group P21/c, Z = 4. The crystal structures were determined by direct methods using multan and refined by least-squares techniques. The tripeptide and the alkylated tripeptide both occur as zwitterions. In the crystalline alkylated peptide, III, the hydrophobic polycyclic groups stack together, in a manner similar to that found in the simple alkylating agent, II. The structure of III consists of layers of aromatic side chains, peptide residues, and water of crystallization. In addition, one of the peptide groups in the alkylated tripeptide is non-planar (torsion angle 159°), possibly a resuit of packing forces in the crystal. The simple peptide I does not crystallize with water of crystallization. The crystal structure involves extensive hydrogen bonding, although a pleated sheet structure is not formed. The zwitterion folds so that part of the structure of the peptide I resembles the conformation found in an α helix. This helicity is lost on alkylation.