Advices For Studying Organic Chemistry

RADIACL REACTIONS

CALICHEAMICIN γ 1 I: A RADICAL DEVICE FOR

SLICING THE BACKBONE OF DNA

1. Calicheamicin γ 1 I binds to the minor groove of DNA where its unusual enediyne
   moiety reacts to form a highly effective device for slicing the backbone of DNA.

1. Calicheamicin γ 1 I and its analogs are of great clinical interest because they are
   extraordinarily deadly for tumor cells.


2. They have been shown to initiate apoptosis (programmed cell death).

2. Bacteria called Micromonospora echinospora produce calicheamicin γ 1 I as a
   natural metabolite, presumably as a chemical defense against other organisms.

NH

I

O

OMe

Me

OMe

S

O

O

OH

HOMe
MeO

Me HN O

HO

O O N O

OH

Me

O

calicheamicin γ 1 I MeO

HO OCO 2 Me

H

O

S

MeSHS

3. The DNA-slicing property of calicheamicin γ 1 I arises because it acts as a
   molecular machine for producing carbon radicals.

1. A carbon radical is a highly reactive and unstable intermediate that has an
   unpaired electron.


2. A carbon radical can become a stable molecule again by removing a proton and
   one electron (i.e., a hydrogen atom) from another molecule.


3. The molecule that lost the hydrogen atom becomes a new radical intermediate.