Synthesis of a novel GC-specific covalent-binding DNA affinity-cleavage agent based on pyrrolobenzodiazepines (PBDs)

SJG-136 (NSC 694501), a Novel Rationally Designed DNA Minor Groove Interstrand Cross-Linking Agent with Potent and Broad Spectrum Antitumor Activity

“…The PBDs have been used as a scaffold to attach EDTA and epoxide moieties, leading to novel sequence-selective DNA cleaving and cross-linking agents, respectively (4,5). In addition, as part of a rational approach to producing more efficient and selective DNA interstrand cross-linking agents, two PBD monomers have been linked together (6).…”

“…The pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs) are a family of naturally occurring antitumor antibiotics, which includes anthramycin, DC-81 ( Fig. 1), tomaymycin, and sibiromycin (1).…”

The newer synthetic strategies for DNA binding pyrrolobenzodiazepine antibiotics (review)

“…Another, new and novel GC-selective pyrrolobenzodiazepine EDTA conjugate has been synthesized recently that covalently binds to DNA at 5'-PuGPu sequence leading to site-specific cleavage. The synthesis of this substance has also been based on the convergent thioacetal deprotection routes [40] (Scheme 17).…”

Pyrrolobenzodiazepines as Sequence Selective DNA Binding Agents

“…EDTA moiety has been linked to the PBD skeleton (DC-81) to study the covalent binding to DNA and its sequence selectivity. [53] Detailed analysis of the cleavage sites by laser densitometry suggested that the results are best explained by two major modes of binding/cleaving for (EDTA/DC-81)Fe II . The EDTA-PBD conjugate covalently binds to DNA at 5′-PuGPu sequences leading to site specific cleavage.…”

“…The research of antineoplastic agents is based on the fact that a single molecule of PBD exhibits higher DNA binding affinity as well as more anticancer activity, if it contains more than one pharmacophore, each with different mode of action and capable of recognizing The PBDs have also been used as a scaffold to attach ethylenediamine tetraacetic acid (EDTA), [49] epoxide, [50] polyamide [51] and oligopyrrole moieties [52] leading to novel hybrids of PBD, which have exhibited sequence selective DNA-cleaving and cross-linking properties. EDTA moiety has been linked to the PBD skeleton (DC-81) to study the covalent binding to DNA and its sequence selectivity.…”