SN1 methylating agents


OTHER NAMES:
SN1 alkylating agents
SN1 reactors
SN1 type mechanism
SN1 type methylating agents


ABBREVIATIONS:
SN1
Sn1


DESCRIPTION: SN1-type agents (e.g. N-methyl-N-nitrosourea, MNU) alkylate both oxygens and nitrogens in nucleic acids.

Methylating agents of the SN1 type represent an important class of cancer chemotherapeutics. Efficient killing by clinically-relevant doses of these agents requires cell division and low levels or absence of the repair enzyme methylguanine methyl transferase (MGMT).
The process requires also an active mismatch repair (MMR) system, as treatment of cells with the prototypic methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) could be shown to trigger a delayed cell cycle arrest, which was absolutely MMR-dependent.

SN1-type agents:
MNU - N-methyl-N-nitrosourea
MNNG - N-methyl-N'-nitro-N-nitrosoguanidine



DNA DAMAGES:
N3-methyl G (3meG)
3-methyl A (3meA)
O6-methyl G (O6meG)
N7-methyl G (7meG)
O2-methyl T (O2meT)
3-methyl A (3-meA) in ssDNA
O2-methyl C (O2meC)
O4-methyl T (O4meT)


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NAME STRUCTURE PROTEINS DNA DAMAGE EFFECT(S) PATHWAY(S) RELATED
N3-methyl G (3meG) AlkA
Tag
ANPG (MPG)
cytotoxic
stalled replication fork
base excision repair (BER)
3-methyl A (3meA) AlkA
Tag
ANPG (MPG)
AP-site
A→T transversion
cell cycle arrest
cytotoxic
mutagenesis
point mutation
stalled replication fork
base excision repair (BER)
O6-methyl G (O6meG) Ada
Ogt
MGMT
G→A transition
mutagenesis
point mutation
substitution
transition
direct reversal (DR)
N7-methyl G (7meG) AlkA
Fpg (MutM)
Tag
ANPG (MPG)
no mutagenesis base excision repair (BER)
O2-methyl T (O2meT) AlkA cytotoxic base excision repair (BER)
3-methyl A (3-meA) in ssDNA AlkA AP-site
A→T transversion
cell cycle arrest
cytotoxic
mutagenesis
point mutation
stalled replication fork
transversion
base excision repair (BER)
O2-methyl C (O2meC) AlkA cytotoxic base excision repair (BER)
O4-methyl T (O4meT) Ogt
Ada
MGMT
cytotoxic
mutagenesis
point mutation
substitution
T→C transition
transition
direct reversal (DR)

References:

  • A comparison of the molecular action of an SN1-type methylating agent, methyl nitrosourea and an SN2-type methylating agent, methyl methanesulfonate, in the germ cells of male mice.
    Sega GA, Wolfe KW, Owens JG.
    Chem Biol Interact., 1981 , : [PUBMED]

Last modification date: Feb. 29, 2012