Control over the sequence specificity of DNA alkylation: syntheses and reactions with 32P-end-labelled DNA of N-alkyl-N-nitrosoureas linked to minor groove binding lexitropsins.
The syntheses of N-2-chloroethyl-N-nitrosoureas (Cl-ENU) that are covalently linked to a series of minor groove binding lexitropsins related to distamycin A are reported. The lexitropsins of 2-Cl-ENU show a sequence specificity for alkylating an adenine toward the ends of its DNA affinity binding domains. The reaction of DNA with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea does not yield these products. Therefore, the linking of the 2-Cl-ENU to the minor groove binder qualitatively and quantitatively alters the DNA observed.
Gold
B
B
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha.
Church
K M
KM
Wurdeman
R L
RL
Zhang
Y
Y
Chen
F X
FX
D000478:Alkylation; D000970:Antineoplastic Agents / Q000378:metabolism*; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D008969:Molecular Sequence Data; D009429:Netropsin / Q000031:analogs & derivatives* / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000378:metabolism*; D010761:Phosphorus Radioisotopes
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D010761:Phosphorus Radioisotopes; C053654:lexitropsin; D009429:Netropsin; D004247:DNA