The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand
cross-links, blocking cell division and resulting in cell death.
Moreover, FANCA has been implicated in the repair of interstrand
DNA crosslinks (3).
Complementation of hypersensitivity to DNA interstrand
crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene.
Patrick, "Role of mismatch repair proteins in the processing of cisplatin interstrand
cross-links," DNA Repair, vol.
One half of the ATPase active site formed by the interstrand
loops of two [beta]-sheets and an a-helix sandwiched between them from one ATPase domain, and the other half is contributed by the [alpha]-helical side of the other ATPase domain .
Excision repair cross-complementation group 1 (ERCC1) is a rate-limiting protein in the nucleotide excision repair and interstrand
crosslink repair pathways, including removing platinum chemotherapy adducts .
The NER pathway, one of the well-known DNA repair pathways, maintains genomic integrity by removing bulky DNA lesions or interstrand
adducts induced by exogenous and/or endogenous factors .
Heaphy, "Evidence for interstrand
quadruplex formation in the dimerization of human immunodeficiency virus 1 genomic RNA," Proceedings of the National Acadamy of Sciences of the United States of America, vol.
Current flow will result in local melting of the a-spots and a rapid increase in interstrand
The company stated VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand
DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death.
Lambert, "Knockdown of [micro]-calpain in fanconi anemia, FA-A, cells by siRNA restores ail spectrin levels and corrects chromosomal instability and defective DNA interstrand
cross-link repair," Biochemistry, vol.
Studies have shown that tilt angle and interstrand
distance for all [beta]-barrel structures vary within a fairly small range .