The reaction of melphalan with deoxyguanosine and deoxyguanylic acid.
The reaction of melphalan (phenylalanine mustard, I) with 2'-deoxyguanosine, followed by removal of the sugar in acid, yielded two products. The major product was identified as 4-(N-(2-guanin-7-ylethyl)-N-(2-hydroxyethyl)amino)phenyl- alanine (II) by ultra-violet absorption, mass and NMR spectroscopy. The minor product has already been identified as the corresponding bis-guaninyl adduct III (Tilby et al., Chem.-Biol. Interact., 73 (1990) 183-194). The reaction of melphalan with 5'-deoxyguanylic acid yielded the deoxyribonucleotide of II and products resulting from reaction with the phosphate group. The initial products, which were formed with a half-life of approximately 40 min at 37 degrees, still had a reactive chloroethyl group; this was displaced more slowly, by reaction with water or with another molecule of dGMP. The products of reaction of melphalan with DNA were released by treatment with acid (0.1 M HCl, 70 degrees, 30 min) and separated from each other on a cation exchange column. They were identified as II, III and an adenine adduct, in a ratio of approximately 3:1:2.
Osborne
M R
MR
Institute of Cancer Research, Haddow Laboratory, Sutton, Surrey, UK.
Lawley
P D
PD
D000478:Alkylation; D004247:DNA / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008558:Melphalan / Q000737:chemistry* / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D003848:Deoxyguanine Nucleotides; D010710:Phosphates; C077233:2'-deoxyguanylic acid; D004247:DNA; D003849:Deoxyguanosine; D008558:Melphalan