2.4.3.3 Peripheral Moieties of the Enediyne Chromophores

As was discussed that the enediyne first bind to the DNA sequence specifically and then breaks the double strand or single strand DNA via the generation of enediyne biradical through the well known BC or MSC that abstract –H from the sugar phosphate backbone of DNA. Now the sequence specific binding of enediyne to DNA and the physical properties of the enediyne chromophores are largely depend on the peripheral moieties encompassing the enediyne warheads. The peripheral moieties or building blocks can be divided into two groups- (a) aromatic and (b) sugar moieties. The aromatic moieties are essential for DNA–chromophore interaction through intercalation. The aromatic unit benzoxazolinate present in C-1027 and orsellenic acid in calicheamicin are found to intercalate into DNA. Besides these aromatic units, many enediyne chromophores contain mono- or polysaccharides that play important roles in fine-tuning the interaction between the chromophore and DNA.

Figure 12. Building blocks of enediyne chromophores. The sites on the enediyne cores for peripheral moiety attachment are indicated by the big dots.

Nature has created the structurally diverse enediyne chromophores, 13 numbers till the date by using a small collection of aromatic and sugar moieties (Figure 12). Connecting these moieties at different positions of the enediyne cores contributes to the structural diversity of enediyne chromophores. More of such aromatic and sugar moieties are expected to discover that will help deciphering new enediyne chromophores in the future.

enediyne cores are given below (Figure 13). Also the successful stories of exploiting the biosynthetic pathways for producing C-1027 and calicheamicin are highlighted.

Figure 13. General biosynthesis of peripheral aromatic moieties of enediynes.