Minor groove, DNA

W. Wierenga "DNA-Minor Groove Binding Anticancer Agents" in Cytotoxic Mnticancer Drugs Models and Conceptsfor Drug Discovey and Development, Kluwer Academic PubHshers, Boston, Mass., 1992, p. 105. 

Schumacher, M.A., et al. Crystal structure of Lac 1 member, PurR, bound to DNA minor groove binding by a helices. Science 266 763-770, 1994. 

Design of DNA minor-groove binders as new antitumor agents 99F15. 

Fig. 3.9 Novel five-membered heterocyclic amino acids that have been incorporated into hairpin polyamides. All residues are shown with the functionality that faces the DNA minor groove towards the bottom-right...

Fig. 3.10 Recognition of the DNA minor groove with benzimidazole derivatives, (a) Structure of the dimeric core for Py-benzimi-dazole (Bi), Py-hydroxybenzimidazole (Hz) and Py-imidazopyridine (Ip) (left) in comparison with the five-membered ring system (right). H-bonding surfaces along the recogni-...

White, S., J.W. Szewczyk, J.M. Turner, E.E. Baird, and P.B. Dervan. Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands. Nature 1998, 393, 468-471. 

Marques, M.A., R. M. Doss, A. R. Urbach, and P. B. Dervan. Toward an understanding of the chemical etiology for DNA minor-groove recognition by polyamides. LLelv. Chim. Acta. 2002, 85, 4485-4517. 

Renneberg, D. and P.B. Dervan. Imida-zopyridine/pyrrole and hydroxybenzimi-dazole/pyrrole pairs for DNA minor groove recognition. /. Am. Chem. Soc. 2003, 125, 5707-5716. 

The DNA minor groove binder brostallicin (PNU-166196, 24), currently in Phase 2 clinical trials for the treatment of soft-tissue sarcoma, exhibited potent... 

Scheme 2.2-9. C2Bio-containing DNA minor groove binders. 

Distamycin A (178) Antibiotic Brostallicin (PNU- Oncology DNA minor groove Phase II Cell Therapeutics 870-877... 

Pommier Y, Kohlagen G BaiUy C, Waring M, Mazumder A, Kohn K. (1996) DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry 35 13303-13309. 

Nearly all structurally characterized DNA polymerases are found to induce B-A transition in DNA bases adjacent to nucleotide incorporation. This induced A-conformation facilitates sufficient access for the protein to desirable contact points in the DNA minor groove. Negative base-pair displacement in the A-form... 

Carteau S, Mouscadet JF, Goulaouic H, Subra F, Auclair C. Inhibition of the in vitro integration of Moloney murine leukemia virus DNA by the DNA minor groove binder netropsin. Biochem Pharmacol... 

It was found that 1 acted as an antimitotic agent, not binding to tubulin, but by disorganizing the microtubule network in some fashion. In addition, it is a DNA minor groove guanine-specific alkylating agent [1]. The Et s showed potent inhibition of DNA and RNA synthesis and of RNA polymerase activity, but its inhibition of DNA polymerase activity is much less marked [75]. The potent activity of Et s was attributed, at least in part, to the unit C since the related saframycin A lacks this unit and has lower efficacy than Et 729 in comparable tumor models [74, 75]. More recent structural information on Et 743-DNA adduct was obtained by NMR spectroscopy [78]. An enantioselective total synthesis of Et 743 has been achieved by Corey et al. [79]. 

The molecular structure of the anticancer drug daunomycin is shown in Fig. 1. It consists of an anthraquinone ring system (aglycon), the portion which intercalates into the DNA [15], and an amino sugar group (daunosamine), which stays in the DNA minor groove. 

---