Ionophores peptides

Eunctionalized supramolecular systems based on monolayers of bioactive compounds (macrocyclic ionophoric peptides, crown ethers, nucleoside derivatives) 98MI12. 

This arrangement gives valinomycin a cavity which exactly fits around the potassium ion giving valinomycin a 10 greater affinity for potassium over sodium ions (Wipf et al., 1970). These types of ionophores have unique abilities to transport metal ions across apolar membranes. The ionophoric peptides have been the subject of two reviews (Hilgenfeld and Saenger, 1982 Lindenbaum ct al., 1979). 

Calcium-binding proteins, 6, 564, 572, 596 intestinal, 6, 576 structure, 6, 573 Calcium carbonate calcium deposition as, 6, 597 Calcium complexes acetylacetone, 2, 372 amides, 2,164 amino acids, 3, 33 arsine oxides, 3, 9 biology, 6, 549 bipyridyl, 3, 13 crown ethers, 3, 39 dimethylphthalate, 3, 16 enzyme stabilization, 6, 549 hydrates, 3, 7 ionophores, 3, 66 malonic acid, 2, 444 peptides, 3, 33 phosphines, 3, 9 phthalocyanines, 2,863 porphyrins, 2, 820 proteins, 2, 770 pyridine oxide, 3,9 Schiff bases, 3, 29 urea, 3, 9... 

A second group of ionophores are considered to promote the formation of cylindrical channels through the membrane. The cation diffuses through the channel from one membrane surface to the other. The known channel-forming ionophores (the open-chain peptide derivative, gramicidin A, is one example) are non-cyclic species and, as such, lie outside the scope of this discussion. 

Interestingly, pretreatment of isolated rat peritoneal mast cells with NT desensitizes the cells to the subsequent stimulation by compound 48/80 (Figure 4.3). However, the desensitized cells are still responsive to stimulation by the calcium ionophore, A23187, in the presence of Ca (Figure 4.3). A similar observation has been made when compound 48/80 and the peptides,... 

In polymorphonuclear leucocytes (PMNL, neutrophils), secretory responses measured as vitamin B -binding protein release were inhibited by feverfew extract when the response was induced by the chemotactic peptide FMLP or arachidonic acid but not when the calcium ionophore A23187 was... 

Howard, T. H. and Wang, D. (1987) Calcium ionophore, phorbol ester and chemotactic peptide-induced cytoskeleton reorganization in human neutrophils. J. Clin. Invest. 79,1359-1364. 

An example of an ionophore that is a cage carrier is valinomycin (9.56). This cyclic peptide lactone consists of three molecules each of L-valine, D-a-hydroxyisovaleric acid, and L-lactate. The six highly polarized lactone carbonyl oxygens line the inside of the ring, whereas the nonpolar alkyl groups point to the outside of the molecule. Thus... 

FIGURE 11-45 Valinomycin, a peptide ionophore that binds K+. In... 

Because the stability constant of its complex with potassium is much greater than that with sodium, valinomycin is a relatively specific potassium ionophore. In contrast, the mushroom peptide antamanide has a binding cavity of a different geometry and shows a strong preference for sodium ions.388,390 The structure of the Na+-antamanide complex is also shown in Fig. 8-22B. The Streptomyces polyether antibiotic monensin (Fig. 8-22D),389,391 a popular additive to animal feeds, is also an ionophore. However, its mode of action, which involves disruption of Golgi functions, is uncertain 392... 

Some 20 years ago it was observed that certain antibiotics could induce the movement of aqueous K+ ions into the mitochondria of cells, but not that of aqueous Na+ ions. These antibiotics, many of which are naturally occurring, are termed ionophores, i.e. neutral molecules which can mediate the transport of the essential groups IA and IIA cations across biological membranes.76 The essential features of an ionophore are a highly polar interior, a hydrophobic exterior and conformational flexibility. Many are cyclic peptides, the coordination properties of the cyclic molecules are considerably different to those of the linear peptides. These differences are outlined in Chapter 20.2. 

A molybdenum-binding ionophore has been described, namely a peptide secreted by Bacillus thuringiensis which can bind MoO ion. Its biological function is not known.81 Curiously the secretion of this peptide appears to occur under conditions of iron depletion. 

A number of ionophores not based on peptides are also known. Again these are microbial metabolites which can bind alkali metal ions and render them lipophilic. Whether all of these function as ionophores in vivo is still to be established in most cases. 

Streptomyces spp. produce both peptide- and non-peptide-based ionophores, the latter type comprising the channel-forming amphotericin B and nystatin. Amphotericin B is a polyhydroxylic lactone which can apparently span half the thickness of a lipid bilayer about 10 molecules are thought to assemble to provide a hydrophilic channel of about 0.5 nm diameter, which allows the passage of small molecules and hydrated metal ions. 

Querfurth, H. W., and Selkoe, D. J. (1994). Calcium ionophore increases amyloid beta peptide production by cultured cells. Biochemistry 33, 4550-4561. 

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