Antibiotics oligopeptide

While much has been learned about the role and selection of the operation parameters in displacement chrcmatography (60-66), little is known yet about the rules of displacer selection and the means available to control the selectivity of the separation. The paucity of well characterized displacers and the lack of knowledge of the solute adsorption isotherms hinder most strongly the wider acceptance and use of displacement chromatography. In most cases, displacer selection is still done by trial-and-error. In the majority of modem displacement chromatographic publications a reversed-phase system was used to separate small polar molecules, antibiotics, oligopeptides and small proteins (52-66). 

The peptaibol antibiotics are a group of linear oligopeptides (of 15 to 24 residues) characterised by the presence of a high content of a-amino isobutyric acid (Aib) residues and an amino alcohol group at the C-terminus. These substances are frequently obtained as a complex mixture of closely related compounds. For example... 

The third current approach is synthesis of peptide chains as models for the helical peptaibol (Section 8.2) and gramicidin (Section 8.3) ion channels. Considerable work has been carried out in the former area, involving synthesis of Aib-containing small peptides, in order to obtain conformational data applicable to the more complex oligopeptide antibiotics. By working with such fragments it has been possible to obtain valuable X-ray crystal structure information on the helical conformation of ala-methin 246), emerimicin 247), suzukacillin 248), and other members of the peptaibol series. 

Tamai, I., et al. The predominant contribution of oligopeptide transporter PepTl to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J. Pharm. Pharmacol. 

Kramer, W., et al. Interaction of renin inhibitors with the intestinal uptake system for oligopeptides and beta-lactam antibiotics. Biochim. Biophys. Acta 1990, 1027, 25-30. 

DKPs, and 2,6-DKPs can be distinguished on the basis of intramolecular C-N cyclization, tandem reactions, and synthetic methods used. 2,3-DKPs have been used in medicinal chemistry and are found in natural products such as antibiotics (piperacillin), cefoperazone, and bicyclomycin. 2,5-DKPs are common namrally occurring peptide derivatives and are frequently generated as unwanted by-products in the synthesis of oligopeptides. " ... 

In situ methods involve the external perfusion of an isolated segment of intestinal tissne." The rat has been shown to be an excellent model for human intestinal permeability." One of the principle advantages of the in situ method is that the intact rat intestinal tissne maintains a normal complement of influx and efQux transporters. Cephalosporins and beta-lactam antibiotics are known to be absorbed by oligopeptide transporters in the GI tract. The rat in situ permeability method was used to determine the saturable Michaelis-Menten-type kinetics for this class of drug molecules. In like fashion, the permeabilities of thymidine anti-viral drugs, like AZT, involving the nncleoside transporter were determined in situ. ... 

Oligopeptide antibiotics and related lexitropsings, synthesis of 890PP1. 4. Vitamins... 

Alkaloids, amides, amines, amino adds, amino phenols, antibiotics, antioxidants, barbiturates, drugs, fatty adds, indole derivatives, nucleobases, oligopeptides, optical brighteners, PAHs, peptides, pharmaceuticals, phenols, phthalates, porphyrins, preservatives, steroids, surfactants, tetracyclines... 

The effect of the oligopeptide antibiotic on the helix-coil transition of DNA is demonstrated by thermal melting of the DNA-distamycin complex. 

Fig. 7 compares the effects of native and denatured DNA, and of RNA on the ultraviolet spectra of the oligopeptide antibiotics containing 3, 4 and 5 pyrrole rings. Three general observations contained in this figure need emphasis. 

In recent years, there has been increasing awareness regarding the importance of transporters in the absorption and disposition of NMEs. While the major portion of NMEs or marketed drugs traverse cell membranes by passive diffusion, there are numerous examples where the involvement of specialized transport mechanisms has been demonstrated. Examples include the role of oligopeptide transporters in the intestinal absorption of P-lactam antibiotics, angiotensinconverting enzyme (ACE) inhibitors, and novel NMEs as well as the role of P-glycoprotein (P-gp) in the secretion of molecules into the intestine [11,77—79]. Transfection of cells with the transporter protein of interest has permitted the evaluation of precise cellular mechanisms of uptake and transport of NMEs. Transfected cell lines by definition are tailor-made to overexpress the protein of... 

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