Peptides membrane-active

Urry, D. W. Nuclear magnetic resonance and the conformation of membrane-active peptides. In Enzymes of Biological Membranes, Vol. 1, (ed. Martonosi, A ), p. 31, Plenum Publishing Corp., New York 1976... 

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Abstract To understand how membrane-active peptides (MAPs) function in vivo, it is essential to obtain structural information about them in their membrane-bound state. Most biophysical approaches rely on the use of bilayers prepared from synthetic phospholipids, i.e. artificial model membranes. A particularly successful structural method is solid-state NMR, which makes use of macroscopically oriented lipid bilayers to study selectively isotope-labelled peptides. Native biomembranes, however, have a far more complex lipid composition and a significant non-lipidic content (protein and carbohydrate). Model membranes, therefore, are not really adequate to address questions concerning for example the selectivity of these membranolytic peptides against prokaryotic vs eukaryotic cells, their varying activities against different bacterial strains, or other related biological issues. 

Keywords Solid-state NMR structure analysis 19F-labeling Membrane-active peptides Native biomembranes Oriented membrane models Antimicrobial peptides... 

Fig. 4 Representative membrane-active peptides that have been studied by solid-state 19F-NMR. (a) The primary sequences show which positions were substituted (filled green boxes) or which ones could in principle be substituted (dotted green lines), (b) Characteristic conformations of the peptides in the membrane-bound state. The space-filling solvent-accessibility models emphasize the amphiphilicity by colouring hydrophobic residues in yellow and cationic side-chains in blue. (c) Observed structures and alignment states of the peptides as determined by 19F-NMR...

Afonin S, Juretic D, Separovic F, Ulrich AS (2011) Special issue on membrane-active peptides. Eur Biophys J 40 347-348... 

Wadhwani P, Strandherg E (2009) Structure analysis of membrane-active peptides using 19F-labeled amino acids and solid-state NMR. In Ojima I (ed) Fluorine in medicinal chemistry and chemical biology. Wiley, Chichester, pp 463-493... 

Wadhwani P, Tremouilhac P, Strandberg E, Afonin S, Grage S, Ieronimo M, Berditsch M, Ulrich AS (2007) Using fluorinated amino acids for structure analysis of membrane-active peptides by solid-state 19F-NMR. In Soloshonok V, Mikami K, Yamazaki T, Welch JT, Honek J (eds) Current fluoroorganic chemistry (ACS symposium series). American Chemical Society, Washington, pp 431 146... 

Grage SL, Afonin S, Ulrich AS (2010) Dynamic transitions of membrane-active peptides. Methods Mol Biol 618 183-207... 

Afonin S (2004) Structural studies on membrane-active peptides in lipid bilayers by solid state 19F-NMR. PhD thesis, University of Jena... 

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Wagner, E. (1999) Application of membrane-active peptides for nonviral gene delivery. Adv. Drug Deliv. Rev., 38, 279-289. 

Lear, J.D., Gratkowski, H., DeGrado, W.F. (2001), De novo design, synthesis and characterization of membrane-active peptides, Biochem. Soc. Transact. 29, 559-564. 

Bong, D. T., Steinem, C., Janshofif, A., Johnson, J. E., and Reza Ghadiri, M. (1999). A highly membrane-active peptide in flock house virus Implications for the mechanism of nodavirus infection. Chem. Biol. 6, 473 81. 

Structure Analysis of Membrane-Active Peptides Using 19F-labeled Amino Acids and Solid-State NMR... 

The cellular membrane is a hydrophobic barrier that surrounds the cytoplasm of every cell and is involved in complex cellular processes, such as signaling and transport, which are essential to maintain the normal life cycle of a cell major components of this cellular membrane are lipids, proteins, peptides, and carbohydrates. Peptides that interact with cellular membranes are referred to as membrane-active peptides and can be broadly divided into three major classes antimicrobial, cell-penetrating, and fusogenic peptides. Any of these may have variable lengths, hydrophobicities, and secondary structures, but they often exhibit similar effects on membranes. For example, some antimicrobial peptides have cell-penetrating properties, and vice versa [23,24] these peptides usually cause some degree of membrane destabilization. 

Figure 18.1 Models for different modes of peptide-lipid interaction of membrane-active peptides. The peptide remains unstructured in solution and acquires an amphipathic structure in the presence of a membrane. The hydrophobic face of the amphipathic peptide binds to the membrane, as represented by the grayscale. At low concentration, the peptide lies on the surface. At higher peptide concentrations the membrane becomes disrupted, either by the formation of transmembrane pores or by destabilization via the "carpet mechanism." In the "barrel-stave pore" the pore consists of peptides alone, whereas in the "toroidal wormhole pore" negatively charged lipids also line the pore, counteracting the electrostatic repulsion between the positively charged peptides. The peptide may also act as a detergent and break up the membrane to form small aggregates. Peptides can also induce inverted micelle structures in the membrane.

To understand the function of membrane-active peptides, it is important to know the structure and orientation of the peptide in the membrane. As is evident from Figure 18.1, it is possible to distinguish between, for example, carpet and pore mechanisms of action by determining the peptide s orientation in the membrane. Various techniques, such as electron spin resonance (ESR) [35], infrared (IR) spectroscopy [36-38], circular dichroism (CD) [35, 39,40], and solid-state NMR (SSNMR) [4-7] are used to investigate membrane-active peptides in a quasi-native lipid bilayer environment. In the following sections, methods to determine peptide structure and orientation are presented. 

Several different 19F-labels with a rigid connection to the peptide backbone, which qualify for 19F NMR according to the criteria described above, were used in our investigations and will now be described in more detail. These amino acids were incorporated into various membrane-active peptides as NMR labels, thereby providing structural information that will be described in Section 18.4. 

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