Neocarzinostatin
Encyclopedia
Neocarzinostatin is a macromolecular chromoprotein
enediyne
antibiotic
with anti-tumor
al activity secreted by Streptomyces macromomyceticus.
It consists of two parts, a labile chromophore
(bicyclic dienediyne structure shown at right) and a 113 amino acid apoprotein
to which the chromophore is tightly and non-covalently bound
with high affinity (Kd ~ 10-10 M). The chromophore is a very potent DNA
-damaging agent; it is very labile and the role of the apoprotein is to protect it and release it to the target DNA. Opening of the epoxide under reductive conditions present in cells creates favorable conditions for a Bergman cyclization
, leading to a diradical intermediate and eventually double DNA strand cleavage. Other members of the neocarzinostatin group of antibiotics are macromomycin, actinoxanthin, kedarcidin and maduropeptin.
As a medicine it is among the most potent, and in Japan only it has been used against liver cancer
clinically.
Chromoprotein
Chromoprotein: A conjugated protein, sulch as hemoglobin, that contains a pigmented prosthetic group, such as hem in hemoglobin . Other examples of chromoprotein are: myoglobin, cytochromes and flavoproteins.In hemoglobin:...
enediyne
Enediyne
Enediynes are a class of bacterial natural products characterized by either nine- and ten-membered rings containing two triple bonds separated by a double bond. Many of these compounds are capable of undergoing Bergman cyclization...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
with anti-tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
al activity secreted by Streptomyces macromomyceticus.
It consists of two parts, a labile chromophore
Chromophore
A chromophore is the part of a molecule responsible for its color. The color arises when a molecule absorbs certain wavelengths of visible light and transmits or reflects others. The chromophore is a region in the molecule where the energy difference between two different molecular orbitals falls...
(bicyclic dienediyne structure shown at right) and a 113 amino acid apoprotein
Apoprotein
Apoprotein can refer to:*Apoenzyme, the protein part of an enzyme without its characteristic prosthetic group.*Apolipoprotein, a lipid-binding protein that is a constituent of the plasma lipoprotein....
to which the chromophore is tightly and non-covalently bound
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
with high affinity (Kd ~ 10-10 M). The chromophore is a very potent DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
-damaging agent; it is very labile and the role of the apoprotein is to protect it and release it to the target DNA. Opening of the epoxide under reductive conditions present in cells creates favorable conditions for a Bergman cyclization
Bergman cyclization
The Bergman cyclization or Bergman reaction or Bergman cycloaromatization is an organic reaction and more specifically a rearrangement reaction taking place when an enediyne is heated in presence of a suitable hydrogen donor . It is named for the American chemist Robert George Bergman...
, leading to a diradical intermediate and eventually double DNA strand cleavage. Other members of the neocarzinostatin group of antibiotics are macromomycin, actinoxanthin, kedarcidin and maduropeptin.
As a medicine it is among the most potent, and in Japan only it has been used against liver cancer
Liver cancer
Liver tumors or hepatic tumors are tumors or growths on or in the liver . Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant...
clinically.