Actinocin

Almost all actinomycins have the same chromophore, a planar phenoxa2inone dicarboxyUc acid called actinocin. In dactinomycin, the stmcture of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-aHo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes /V-methyl isoleucine instead of /V-methylvaline. The lactone ring is always present. 

Actinocin — see Phenoxazine-l,9-dicarboxylic acid, 2-amino-4,6-dimethyl-3-oxo-Actinoleutin applications, 3, 195 Actinomycins... 

Amino-4,6-dimethyl-3-oxo-3//-phenoxazine-l,9-dicarboxylic acid also named actinocin is the chromophor of the red antineoplastic chromopeptide aetinomyein D (formula A). Two cyclopenta-peptide lactone rings (amino acids L-threonine, D-valine, L-proline, sarcosine, and 7V-methyl-L-valine) are attached to the carboxy carbons of actinocin by two amide bonds involving the amino groups of threonine. 

Evaluation of the HH ROESY (c) verifies the amino acid sequence of the cyclopentapeptide lactone ring attached to C-9 of actinocin by means of the NOE induced spatial correlation signals la-belled a d in the formula C. The a- and (3-protons of threonine in both cyclopentapeptide lactone rings are sufficiently separated but close to each other. This applies to the other amino acid protons with the exception of TV-methylvaline, in which proton signals overlap (Table 55.1). Therefore, starting from the a- and [3-protons of threonine 8H = 4.61 and 5.75), the sequence Thr-Vai-Pro-Sar-MeVal attached to C-l of actinocin is similarly verified in the HH ROESY as shown in formula C. The connection Sar-MeVal is established by the spatial correlations d between the 72-protons of sarcosine and the A7-methyl-protons of 7V-methylvaline in both rings (SH = 4.71/2.92 and 4.78/2.89). 

The attachment of the cyclopentapeptide lactone rings to the carboxy functions at C-1 and C-9 of the actinocin heterocycle B can be deduced from the HMBC plot d Protons 1-H (Sh = 7.35) and S-H Sh = 7.62) of the heterocycle display an AB system in the proton domain. The attached carbon nuclei have been assigned by CH COSY in the literature (5///5c = 7.55/130.33 and 7.(52/125.93, ref p. 426) the other carbon atoms of the benzenoid ring within the phenoxazone are assigned as reported by correlation via Jqh and Vc// coupling detected in d which additionally shows a weak Jqh correlation signal of 8-iTwith C-5a (5///5c = 7.(52/140.53). 

Actinomycins are chromopeptides, generally containing the same chro-mophore, based on the tricyclic system of phenoxazinone (phenoxazone), and known as actinocin, Fig. (8). The chromophore is responsible for the intense yellow, orange or red colours of actinomycins. The first known actinomycin was isolated from a culture medium of an actinomyces, Streptomyces sp. [174], and caused some interest on account of its antibiotic activity. Many other actinomycins were isolated later and characterised by their antibiotic and/or antitumor activities [175]. Among these, the best known is actinomycin D (Dactinomycin), Fig. (8). 

CA and actinocin, and the intercalating properties of the latter, prompted Nair [195] to hypothesise the existence of a regulatory mechanism for RNA synthesis, involving the oxidative dimerisation of HA. Following this suggestion, CA could specifically interact with DNA, preferably on guanine residues, such as actinomycin D does [196]. This was confirmed by the observation, that either preformed CA and HA (converted to CA by the nuclear fraction) were actually bound by DNA, in correspondence with guanine residues. However, no data exist about the actual formation and concentration of CA within the rat liver. 

The binding of the actinocin and polypeptide lactone portions of dactinomycin to DNA is cooperative, meaning that the binding of one unit facilitates the binding of the other, most likely by promoting an optimal... 

Actinomycins, peptide antibiotics produced by various strains of Streptomyces. Actinomycins are orange-red bacteriostatic and cytostatic, but highly toxic, chromopeptides. The chromophore actinocin,... 

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