Antibacterial specific

Antimicrobial Activity. The elfamycins antimicrobial specificity and lack of toxicity in animals can be explained in view of species-dependent specificity of elfamycin binding to EE-Tu. Inefficient cellular uptake or the presence of a nonresponding EE-Tu were cited as responsible factors for the natural resistance in Halohacterium cutiruhrum (67), Lactobaci//us brevis (68), and in actinomycetes (5,69). The low activity of elfamycins against S. aureus was also attributed to an elfamycin-resistant EE-Tu system (70). However, cross-resistance with other antibacterial agents has not been observed (71). 

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

Product specifications for microbial food enzymes have been estabUshed by JECEA and ECC. They limit or prescribe the absence of certain ubiquitous contaminants such as arsenic, heavy metals, lead, coliforms, E. coli and Salmonella. Furthermore, they prescribe the absence of antibacterial activity and, for fungal enzymes only, mycotoxins. 

The biochemical basis of penicillin action continues to be an area of active investigation. Penicillins are highly specific inhibitors of enzyme(s) involved in the synthesis of the bacterial cell wall, a structure not present in mammalian cells. Three principal factors are thought to be important for effective antibacterial action by a penicillin ... 

The inhibitors of RNA polymerase, which generates RNA from DNA, inhibit a crucial step in gene expression. Inhibition of the eukaryotic form of RNA polymerase is used in cancer chemotherapy and is also an important experimental tool. For example, actinomy-cin D binds to the guanine residues in DNA and blocks the movement of the eukaryotic RNA polymerase. Specific inhibitors of bacterial RNA polymerase can be used as antibacterial agents. Most of these inhibitors like rifamycin bind to the prokaryotic enzyme. 

Tenecteplase (TNKase) is the first thrombolytic drug that can be administered during a period of 5 seconds in a single dose The drug is administered intravenously only and offers the fastest administration of a thrombolytic in the treatment of an acute MI. Specific instructions for reconstitution come with the drug. The drug is reconstituted immediately before use because it contains no antibacterial preservatives. 

As such, the magainins provide a useful initial target for peptoid-based peptido-mimetic efforts. Since the helical structure and sequence patterning of these peptides seem primarily responsible for their antibacterial activity and specificity, it is conceivable that an appropriately designed, non-peptide helix should be capable of these same activities. As previously described (Section 1.6.2), peptoids have been shown to form remarkably stable hehces, with physical characterishcs similar to those of peptide polyprohne type-I hehces (e.g. cis-amide bonds, three residues per helical turn, and 6A pitch). A faciaUy amphipathic peptoid helix design, based on the magainin structural motif, would therefore incorporate cationic residues, hydrophobic aromatic residues, and hydrophobic aliphathic residues with threefold sequence periodicity. 

The renaissance of the Biginelli MCR can be attributed to the obtained pyrimidine derivatives, which show remarkable pharmacological activity. A broad range of effects, including antiviral, antitumor, antibacterial, anti-inflammatory as well as antihypertensive activities has been ascribed to these partly reduced pyrimidine derivatives [96], such as 9-117 and 9-118 (antihypertensive agents) [97] and 9-119 (ala-adrenoceptor-selective antagonist) [98] (Scheme 9.24). Recently, the scope of this pharmacophore has been further increased by the identification of the 4-(3-hydroxyphenyl)-pyrimidin-2-thione derivative 9-120 known as monastrol [98], a novel cell-permeable lead molecule for the development of new anticancer drugs. Monastrol appears specifically to affect cell division (mitosis) by a new mechanism,... 

Silver and mercury salts have a long history of use as antibacterial agents.241-243 The use of mercurochrome ((40), Figure 18) as a topical disinfectant is now discouraged. Silver sulfadiazene (38) finds use for treatment of severe burns the polymeric material slowly releases the antibacterial Ag+ ion. Silver nitrate is still used in many countries to prevent ophthalmic disease in newborn children.244 The mechanism of action of Ag and Hg is through slow release of the active metal ion—inhibition of thiol function in bacterial cell walls gives a rationale for the specificity of bacteriocidal action. 

Nishimura, Y., Adachi, H., Kyo, M., Murakami, S., Hattori, S., and Ajito, K. (2005) A proof of the specificity of kanamycin-ribosomal RNA interaction with designed synthetic analogs and the antibacterial activity. Bioorg. Med. Chem. Lett. 15, 2159-2162. 

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