Nogalamycines

Galea AM, Murray V (2002) The interaction of cisplatin and analogues with DNA in reconstituted chromatin. Biochim Biophys Acta 1579(2-3) 142-152 Ganguli R, Chowdhury K, Chakraborty B, Neogy RK (1983) Interaction of nogalamycin with chromatin. Chem Biol Interact 46(3) 347-352... 

ESI-MS was also successfully employed for the analysis of very weak noncovalent drug/duplex DNA complexes. The DNA complexes of nogalamycin, which contains the 1,3-dioxane moiety, and of several analogs were detected this way <1998MI342, 1999RCM2489, 2002CC556>. 

In addition to electrophilic functionalization, the 5,6-double bond of the adducts (see (222)) is reported to undergo high-pressure [4 + 2]-cycloaddition with jV-(2,4-dinitrophenyl)isoquinolinium chloride (223) (Bradsher cycloaddition) to afford the naphthol-substituted isoxazoline (224) (Equation (61)), which was used for the total synthesis of nogalamycin analogues <92JOC644>. 

Allyl bromide, methyl iodide and benzyl bromide are the triumvirate of common alkyl halides that alkylate metal alkoxides readily. In the case of phenols, potassium carbonate [Scheme 4.230]438 or cesium carbonate are competent bases whereas primary and secondary alcohols require potassium hydroxide [Scheme 4.231J,402 but the strongly basic conditions limit the scope of the method. For example, attempts to alkylate the secondary and phenolic hydroxyl groups of the intermediate 232.1 in a synthesis of the antibiotic Nogalamycin using the traditional metal alkoxide alkylation failed owing to competing sec-... 

The largest number of solution structures reported involves modified DNA structures, including a number of duplexes binding to small molecules. A number of structures are reported complexed to various antibiotics, including actinomycin distamycin, phleomycin and nogalamycin. " ... 

Nogalamycine, which contains two sugars (one attached to the D-ring and the second attached at C-7 of the A-ring), binds to DNA in a slightly different manner [31]. 

The results obtained by various workers employing these several techniques are not in total agreement. It seems clear, however, that the presence of deoxyguanosine residues in DNA is required for binding of Actino-mycin D. Anthracyclines can complex with poly dAT and poly dGdC however, binding of nogalamycin may be favored by dAT pairs while that of daunomycin is not. The presence of cations (Mg" or Cs" ) may play a role in complex formation between the chromomycin antibiotics and DNA. 

H. E. L. Williams and M. S. Searle, Structure, dynamics and hydration of the nogalamycin-d(ATGCAT)2 complex determined by NMR and molecular dynamics simulations in solution, J. Mol. Biol. 290, 699-716 (1999). 

---