Actinomycin properties

Other agents such as actinomycin D, C-Myc antisense, dexamethasone, and matrix metalloproteinase inhibitors, aimed at altering inflammatory and smooth muscle actions in the biological repair response to vascular injury, are being evaluated. The success of these devices depends upon multiple issues, including stent platform, carrier, drug properties, and pharmacokinetic profile (18-26). Large randomized, controlled trials, demonstrate a restenosis rate of 5% to 10% with DES (27). 

A number of antibiotics possess pronounced cytostatic properties, and they are extremely effective in treating certain tumors. Included in this group are actinomycin, anthracyclins (daunorubicin and doxorubicin), bleomycin, and others. 

Pyrolysis of simple peptides offers models for understanding the pyrolysis results of larger polypeptides and proteins. Also, special types of peptides of practical interest are those with antibiotic properties such as the actinomycins containing peptide side-chains, etc. Their pyrolysis has been proven to be useful for structure elucidation and identification [9]. Other polypeptides with therapeutic use such as lypressin and felypressin were also studied by pyrolysis [10]. 

Polypeptide pyrolysis is important in connection with protein pyrolysis, but some studies were done on particular peptides such as actinomycins, which have antibiotic and cytostatic properties. Several actinomycins are known, the formulas for some of them being represented by ... 

RECEPTOR AGONIST used aS an ANTIPARKINSONIAN AGENT. It iS also a PROLACTIN RELEASE INHIBITOR, cachectin tumour necrosis factor, cactinomycin actinomycin C. cadralazine [ban. inn.jan] has properties similar to hydralazine. It is a VASODILATOR and formerly used as an ANTIHYPERTENSIVE. 

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. 

Dactinomycin, or actinomycin D as it was called when first introduced, has shown striking curative properties in Wilms s tumour of the kidney which forms a high proportion of all malignant tumours in children. Under its influence, even pulmonary metastases caused by this tumour regress (Farber and Mitus, 1968). Forms of cancer requiring longer treatment are not suitable for this drug, which has only moderate selectivity. 

Electron microscopic observations have shown that the cells of isolated gastrula ectoderm after some days in culture develop in their periphery a zone which contains vacuoles and in some cells the basal bodies of cilia. These are the same structures as found in epidermis. They are not found in the ectoderm, which was induced by the vegetalising factor. Obviously gastrula ectoderm is already determined to special pathways during differentiation, but its developmental fate can still be changed. In ectoderm treated with actinomycin D the vacuolar zone is retarded in its development (Grunz, 1973). A more general problem is raised by these experiments. Obviously, the induction of the ectoderm leads not only to an acquisition of new properties but also to a loss of properties which would have been expressed in the uninduced ectoderm. 

Fawaz F, Jones CH. Actinomycin synthesis in Streptomyces ontibiotinu Purification and properties of hydroxYanthranilate-4 mechylcransfetase. ] Biol Chem 1988 263 4602-4606. Jones GH. Combined purification of actinomycin synthetase I and 3-hydroxyanthranilic acid 4-methylttansferase from Streptamyces aruibi rmcus. ] Biol Chem 1993 268 6831-6834. Keller U, Schlumbohm W. Purification and characterization of actinomycin synthetase I. a 4 methy -3-hydroxyanthranilic acid AMP ligase from Streptomjees chrysomallus. J Biol Chem 1992 267 11745-11752. 

The platelets contain a contractile protein (throm-bosthenin), which has solubility properties similar to those of the actomyosin group of proteins. The activity of the protein requires the presence of ATP and metallic ions. The protein has been isolated from human platelets, and like actinomycin, the contractile protein possesses ATPase activity. Electron microscopic examination of isolated thrombosthenin revealed a microfibric structure 80-100 A wide with a possible periodic structure [28]. In the presence of ATP, the contractile protein dissociates into an actinlike protein (thrombosthenin A) and a myosinlike (thrombosthenin M) moiety. ATPase activity is nonexistent in thrombosthenin A and weak in thrombosthenin M. When tested alone, neither thrombosthenin A or M is ATP sensitive, but the mixing of A and M thrombosthenin restores ATP sensitivity and ATPase activity. 

In contrast to the biocatalytic potential of the MTs, which already have been applied in enzyme cascades, that of a number of enzymes with exceptional substrate specificity or catalytic properties has not been fiiUy exploited. This is especially tme for C-methyltransferases, which catalyze the challenging Friedel-Crafts methylation of phenols [102], tyrosine, or coumarine derivatives (M. Tengg et al, unpublished results), or antibiotics such as actinomycin [103]. 

A detailed description of the chemical properties of actinomycin C and of several of its derivatives can be found in the publication of Brockmann et al. (94). Let us merely point out here that we are dealing with one or more closely related cyclic peptides, of molecular weight around 1200, which do not react with ninhydrin nor possess free —NH2 groups (94). 

Table 1 shows the viscosity and sedimentation data obtained for anthramycin DNA complexes using DNA of various molecular weights. The molecular weight of DNA used in these measurements was varied because of the observation of Muller and Crothers on Actinomycin-D complexes which indicated that the hydrodynamic properties of the com-... 

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