Biomaterial Database

Mechanisms of DNA sequence selective alkylation of guanine-N7 positions by nitrogen mustards. 1987

K W Kohn, and J A Hartley, and W B Mattes

Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD.

Quantitative determinations were carried out of the relative reaction rates of several nitrogen mustards at various guanine-N7 positions in DNA fragments of known sequence. The findings suggest structural hypotheses of the origins of the reaction selectivities. End-labeled DNA fragments were reacted with nitrogen mustards, and the guanine-N7 alkylation sites were analyzed by gel electrophoresis. Relative reaction intensities were determined by computer analysis of digitized densitometer scans. The differences in reaction intensities at different G's were in part attributable to the effects of nearest neighbor base pairs on the molecular electrostatic potential near the reaction site. Uracil and quinacrine mustards have specific sequence preferences for reaction that differ from other mustards. The nature of the specific sequence preferences were determined and hypotheses are proposed to explain their origin.

UI	MeSH Term	Description	Entries
D009588	Nitrogen Mustard Compounds	A group of alkylating agents derived from mustard gas, with the sulfur replaced by nitrogen. They were formerly used as toxicants and vesicants, but now function as antineoplastic agents. These compounds are also powerful mutagens, teratogens, immunosuppressants, and carcinogens.	Compounds, Nitrogen Mustard,Mustard Compounds, Nitrogen
D002412	Cations	Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.	Cation
D002627	Chemistry, Physical	The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.	Physical Chemistry,Chemistries, Physical,Physical Chemistries
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006147	Guanine
D000478	Alkylation	The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.	Alkylations
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D055598	Chemical Phenomena	The composition, structure, conformation, and properties of atoms and molecules, and their reaction and interaction processes.	Chemical Concepts,Chemical Processes,Physical Chemistry Concepts,Physical Chemistry Processes,Physicochemical Concepts,Physicochemical Phenomena,Physicochemical Processes,Chemical Phenomenon,Chemical Process,Physical Chemistry Phenomena,Physical Chemistry Process,Physicochemical Phenomenon,Physicochemical Process,Chemical Concept,Chemistry Process, Physical,Chemistry Processes, Physical,Concept, Chemical,Concept, Physical Chemistry,Concept, Physicochemical,Concepts, Chemical,Concepts, Physical Chemistry,Concepts, Physicochemical,Phenomena, Chemical,Phenomena, Physical Chemistry,Phenomena, Physicochemical,Phenomenon, Chemical,Phenomenon, Physicochemical,Physical Chemistry Concept,Physicochemical Concept,Process, Chemical,Process, Physical Chemistry,Process, Physicochemical,Processes, Chemical,Processes, Physical Chemistry,Processes, Physicochemical