Peptides ionophoric properties

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. 

Model systems have been developed for many of these ion-transport mechanisms in the context of bioorganic chemistry. Examples are the cyclic peptides, described by M. R. Ghadiri et al., that have antibiotic activity similar to that of ionophores, a property that is most probably caused by the ability of these peptides to self-assemble inside biological membranes into channels [1], Other compounds able to induce the formation of membrane pores are the bouquet-molecules introduced by J.-M. Lehn [2]. Artificial / -barrels have been developed by S. Matile s group [3]. Many host molecules used in bioorganic chemistry can serve as carriers for ions across membranes and have even made possible the development of systems with which active ion transport can be achieved [4]. 

This technique essentially comprises two aqueous compartments containing electrolyte connected by a pinhole across which a bilayer of phospholipid molecules is spread. An electrical potential is applied across the bilayer and in the presence of an ionophore the resultant current flowing between the two chambers is measured as a function of time.12 The method is often used to assess the activity of synthetic peptides, and has been used to measure the channel activity of several non-peptide channels. Of particular significance is its use in allowing the measurement of the single channel properties of isolated channel-forming proteins that have been reintroduced back into planar bilayer membranes.13... 

Engstrom I, Ronquist G, Pettersson L, Waldenstrom A (1995) Alzheimer amyloid beta-peptides exhibit ionophore-fike properties in human erythrocytes. Eur J CUn Invest 25 471 76... 

Biological membrane channels are formed not only by integral membrane proteins like porine but also by certain peptides antibiotics called ionophores that vastly increase the permeability of membranes to particular ions. " The antibiotic properties of ionophores arise from their tendency to discharge vital concentration gradients. The... 

Peptide alkaloids were first studied because of their therapeutic, antibiotic properties. There is some evidence that peptide alkaloids may serve as ionophores in the plant and... 

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