What does calicheamicin do?
Calicheamicin is a potent cytotoxic agent that causes double-strand DNA breaks, resulting in cell death (Dedon et al., 1993; Drak et al., 1991; Zein et al., 1988).
Why is calicheamicin effective in treating myeloid leukemia?
6, has been chosen to target the potently cytotoxic calicheamicin antitumor antibiotics to acute myeloid leukemia (AML) due to the presence of CD33 on >80% of patient samples and its lack of expression outside the myeloid cell lineages, especially its lack of expression on pluripotent stem cells.
Is calicheamicin an alkyne?
[*] Calicheamicin is part of a class of toxic chemicals called Alkynes, which are generally not very useful as pharmaceuticals. These molecules are cyclic and contain an alkene (double bond) in between two alkyne (triple bonds) functions, therefore the name ene < alkene and diyne < two alkynes.
Which temperature is suitable for carried out Bergman cyclization?
around 200 °C
Mechanism of the Bergman Cyclization. The cyclization is induced thermally or photochemically. Most cyclizations have a high activation energy barrier and therefore temperatures around 200 °C are needed for the cycloaromatization.
Where are alkynes found?
Small amounts of alkynes are found in crude oil and natural gas. However, alkynes found in nature in plants and in some animals possess physiological functions.
Which of the following is ah donor in a Bergman cyclization?
The Bergman Cyclization allows the construction of substituted arenes through the thermal or photochemical cycloaromatization of enediynes in the presence of a H• donor such as 1,4-cyclohexadiene.
What is the meaning of cyclization?
: formation of one or more rings in a chemical compound.
How does calicheamicin cause double strand DNA break?
Calicheamicin is a cytotoxic agent that causes double-strand DNA breaks. PF-06647263 (anti-EFNA4-ADC) is generated via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-γ1 linker-payload with an average drug-to-antibody ratio (DAR) of 4.6.
How is calicheamicin reduced to a diradical?
After binding to the minor groove of DNA with some sequence specificity, calicheamicin is reduced by cellular thiols. The resultant product undergoes rearrangement to generate a 1,4-dehydrobenzene diradical that abstracts hydrogen atoms from DNA, thereby initiating double-strand cleavage ( Scheme 5.9 ).
How is calicheamicin a natural anticancer agent?
Calicheamicin represents one of the most structurally complex natural products that has been developed into an anticancer agent. The compound was isolated from the fermentation broth of a bacterium, Micromonospora echinospora ssp. calichensis.
Which is an antibody conjugated with calicheamicin?
Gemtuzumab ozogamicin (Mylotarg ®) is an anti-CD33 antibody conjugated with calicheamicin, a potent antitumor antibiotic. This agent binds to the CD33 antigen, which is highly expressed on the surface of the majority of APL cells universally.