Transport antibiotics

Law et al. [15] determined the diffusion coefficient for benzyl penicillin in thin films of Palacos, Simplex and CMW cements assuming that antibiotic transport can be described by Fick s law using a finite difference approximation to quantify transient non-steady-state behaviour. These investigators found that the diffusion coefficient was increased in the presence of additives and proposed that the finite difference approach could be applied to determine release of antibiotic from preloaded PMMA beads. Dittgen and Stahlkopf [16] showed that incorporation of amino acids of varying solubilities also affected release of chloramphenicol from polymethacrylic... 

Siderophores -role m antibiotic transport [ANTIBIOTICS - BETA-LACTAMS - CEPHALOSPORINS] (Vol 3) - [ANTIBIOTICS - PEPTIDES] (Vol 3) -iron compounds of [IRON COMPOUNDS] (Vol 14)... 

J Trias. Antibiotic transport in mycobacteria. In N Georgopapadakou, ed. Drug Transport in Antimicrobial and Anticancer Chemotherapy. New York Marcel Dek-ker, 1995, pp 269-288. 

Tamao, I. Tomizawa, N. Takeuchi, T. Nakayama, K. Higashida, H. Tsuji, A. Functional expression of transport of intestinal dipeptide/P-lactam antibiotic transporter in Xenopus laevis oocytes. Biochem. Pharmacol. 1994, 48, 881-888. 

In addition to the 47 resistance genes mcr and mrd, with wrd linked to mitA, a third 47 resistance component, met, 5 kb upstream of mrd was found, met is a putative 47 tranlocase encoding a presumed antibiotic transporter it encodes a 484 amino acid protein with 14 predicted transmembrane domains. 

Two genes, rebU and rebT, could participate in rebeccamycin resistance and/or secretion. The deduced product of rebU is similar to a family of Na /H+ exchange membrane proteins which function as antiporters of Na" " or K" " and H+ and play a key role in maintaining cellular pH and other processes. RebU was found to be most similar to a putative integral membrane ion antiporter and antibiotic transporter. The second candidate for rebeccamycin resistance and/or secretion, the rebT gene... 

The epithelial Uning fluid of the lung is separated by the nonfenestrated capillary endothelium on one side and alveolar membrane on the other both are permeable to lipid-soluble antibiotics such as macrolides, quinolones, clindamycin, and trimethoprim-sulfamethoxazole, but relatively impermeable to water-soluble agents such as the aminoglycosides and P-lactams. However, the contribution of antibiotic transport of the water-soluble agents by polymor-... 

The mechanism of inhibition has not been characterized, but it is probably related to the ionophoretic properties of these antibiotics. Monensin has been shown to inhibit the intracellular transport of viral membrane proteins of cells infected with Semliki Forest vims (169). The formation of syncytia, normally observed when T-lymphoblastoid cell line (CEM) cells are cocultivated with human immunodeficiency vims (HlV-l)-infected T-ceU leukemia cell line (MOLT-3) cells, was significantly inhibited in the presence of monensin (170). This observation suggests that the viral glycoproteins in the treated cells were not transported to the cell surface from the Golgi membrane. 

In order to prevent veterinary dmgs from being transported to the human food chain, radioisotopic immunoassays were developed to monitor veterinary antibiotics such as penicillin and chloramphenicol [56-75-7] C22H22Cl2N20, in meat, milk, and eggs (qv) (see ANTIBIOTICS Meatproducts Milk AND MILKPRODUCTS). 

MacrotetroHdes of the valinomycin group of electrically neutral antibiotics form stable 1 1 complexes with alkaH metal ions that increase the cation permeabiHty of some biological and artificial lipophilic membranes. This solubiHzation process appears to have implications in membrane transport research (30) (see Antibiotics, peptides). 

The antibiotic aplasmomycin serves as a receptor or transporter for borate. Retrosynthetic simplification of the boron-free macrocycle to identical hydroxy acid subunits is clearly appropriate. Further retrosynthetic dissection produced fragments A, B and oxalate and provided a workable synthetic plan. 

Bradshaw and his coworkers have listed several motivations for their explorations in this area. One objective of [the] research program is to prepare and study a series of multi-dentate compounds which resemble naturally occurring macrocyclic compounds . Further, Bradshaw and his coworkers have said that it is our hope that we can prepare macrocycles to mimic the selectivities of the naturally occurring cyclic antibiotics and thereby make available models for the investigation of biological cation transportation and selectivity processes . These workers have presented a number of comparisons with valinomy-cin . The other expressly stated goal of their research is to prepare molecules which will allow us to systematically examine the parameters which affect complex stability and to understand that stability in terms of AH and TAS values for complex formation . 

A second source of inspiration for studying the open-chained equivalents of crown ethers was the observation that a number of naturally occurring antibiotics enhance cation transport and bear a structural similarity to open-chained crown ethers. A number of groups have examined neutral synthetic ionophores and a variety of novel cation carriers is now available. This is discussed in Sect. 7.4, below. 

In addition, several oj-hydroxyacids have been prepared. The systems prepared by Yamazaki (8) have been evaluated for ion transport action. Those prepared at Upjohn have been reported to have Ca activity comparable to the natural antibiotic X-537A (9) and to be more active than crown ethers. The most active of their structures is shown as 10. 

All of the transport systems examined thus far are relatively large proteins. Several small molecule toxins produced by microorganisms facilitate ion transport across membranes. Due to their relative simplicity, these molecules, the lonophore antibiotics, represent paradigms of the mobile carrier and pore or charmel models for membrane transport. Mobile carriers are molecules that form complexes with particular ions and diffuse freely across a lipid membrane (Figure 10.38). Pores or channels, on the other hand, adopt a fixed orientation in a membrane, creating a hole that permits the transmembrane movement of ions. These pores or channels may be formed from monomeric or (more often) multimeric structures in the membrane. 

Monensin, which is one of the natural antibiotics, selectively transports Na+ across an artificial liquid membrane (organic solvent) from the basic aqueous phase (IN) to the acidic aqueous phase (OUT), driven by the proton gradient8). (Fig. 1, 2)... 

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