Amphiphilic helices

Burkoth, T. S., Beausoleil, E., Kaur, S., Tang, D., Cohen, F. E., and Zuckermann, R.N. Toward the synthesis of artificial proteins The discovery of an amphiphilic helical peptoid assembly. Chem. Biol. 2002, 9, 647-654. 

Arakawa, R., Hayashi, M., Remaley, A. T., Brewer, B. H., Yamauchi, Y. and Yokoyama, S. Phosphorylation and stabilization of ATP binding cassette transporter Al by synthetic amphiphilic helical peptides. /. Biol. Chem. 279 6217-6220,... 

An alternative efficient approach to disperse CNTs relies on the use of synthetic peptides. Peptides were designed to coat and solubilise the CNTs by exploiting a noncovalent interaction between the hydrophobic face of amphiphilic helical peptides and the graphitic surface of CNTs (Dieckmann et al., 2003 Zoibas et al., 2004 Dalton et al., 2004 Arnold et al., 2005). Peptides showed also selective affinity for CNTs and therefore may provide them with specifically labelled chemical handles (Wang et al., 2003). Other biomolecules, such as Gum Arabic (GA) (Bandyopadhyaya et al., 2002), salmon sperm DNA, chondroitin sulphate sodium salt and chitosan (Zhang et al., 2004 Moulton et al., 2005), were selected as surfactants to disperse CNTs (Scheme 2.1). 

Polymeric phospholipids based on dioctadecyldimethylammonium methacrylate were formed by photopolymerization to give polymer-encased vesicles which retained phase behavior. The polymerized vesicles were more stable than non-polymerized vesicles, and permeability experiments showed that vesicles polymerized above the phase transition temperature have lower permeability than the nonpolymerized ones [447-449]. Kono et al. [450,451] employed a polypeptide based on lysine, 2 aminoisobutyric acid and leucine as the sensitive polymer. In the latter reference the polypeptide adhered to the vesicular lipid bilayer membrane at high pH by assuming an amphiphilic helical conformation, while at low pH the structure was disturbed resulting in release of the encapsulated substances. 

The presence of bulky, (3-branched side chains can be helix promoting or destabilizing depending on the environment. 100 The role of hydrophobic residues in helix stabilization has been studied in Ala-based peptides 106 as well as through Monte Carlo calculations. 107 The positioning of hydrophobic residues is also important. In amphiphilic helices, hydrophobic residues repeat approximately every three to four residues, such that one side of the helix is hydrophilic and one side hydrophobic. The amphiphilicity makes the peptide susceptible to helix formation in the presence of lipid-water interfaces. 108 109 ... 

In addition to finding small organic molecules that bind to a protein, covalent capture methods can identify peptides that interact with proteins. Kohda and colleagues used this approach to study the mitochondrial protein Tom20, an import receptor that recognizes an epitope on proteins targeted for the mitochondria.1301 Previous work had characterized this epitope as a five-residue peptide that assumes an amphiphilic helical conformation, and coarse sequence preferences had been worked out. However, Tom20 has both low affinity... 

A photoresponsive amphiphilic helical polypeptide (a helical polypeptide in which all the polar residues are located on one side of the helical cylinder and all the hydrophobic residues on the opposite side) was prepared by Higuchi et al., using a simple and unique technique.1117-1211 The polypeptide XXI was first placed at a... 

Fig. 18 Schematic illustration of the preparation and photoresponsive behavior of the polypeptide XXIII, consisting oftwo amphiphilic helical rods linked by an azobenzene unit, a) Selective saponification of COOCH3 side...

The compound XXIII, consisting of two amphiphilic helical rods linked by an azobenzene moiety, was found to form micelles and ordered aggregates in aqueous solution in the dark, when the azo moiety is in the trans configuration. Photoisomerization of the azo linkage into the cis configuration, and the consequent bending in the structure of the molecules, induced disaggregation and disruption of the micelles.1118,1191... 

Fig. 3.17. Amphiphilic secondary structures. By specifying the locations of polar (light gray) and nonpolar (dark gray) residues through simple binary patterns, amphiphilic helical or pi-sheet structures can be designed [154].

By inserting appropriate amino acid side chains (e.g., hydrophilic and hydrophobic), it is feasible to construct amphiphilic helices (with two faces that possess different properties). The conformational strategy should take into account the parameters typical of each of the two helices, in particular that 1) The a-helix (Fig. la) is characterized by a fractional number of amino acids per turn (=3.5) and consequently its smallest repeat (i.e., the shortest main-chain length that brings two side chains exactly one on top of the other) is a heptad (7 residues) and 2) in the 3io-helix (Fig. lb), which has an integer number of amino acids per turn (=3.0), a triplet of residues selected carefully will produce the expected amphiphiUcity. 

The amphiphilic helical structure of most antibacterial peptides is a prerequisite for theu propensity to form chaimels across the double-layered biological membranes (12). In aqueous solution, positions a and d of the a-helical heptad repeat (a, b, c, d, e, f g) ( 3) require hydrophobic residues for the onset of the widespread antiparallel dimer (or multimer) superstructure (a-helix coiled coU) (14—16) (Fig. 2). The hydrophilic positions e and g, immediately on the back, reinforce the dimer stability... 

Tang and co-workers used leucine-functionalized phenyl acetylene derivatives for the construction of amphiphilic helical polymers, which were envisioned to be both semi-conducting and biocompatible, leading to diverse applications such as biosensors [36]. The polymerization was performed with a rhodium catalyst and resulted in high molecular weight polymers, particularly for polyacetylene la (1.5 10 g/mol). Interestingly, only the polymers in which the stereo-center was closely located to the helical backbone (la and lb) showed a CD signal and were optically active (Fig. 6). 

Patent Number US 5847047 A 19981208 ANTIMICROBIAL COMPOSITION OF APOLYMER AND A PEPTIDE FORMING AMPHIPHILIC HELICES OF THE MAGAININ-TYPE... 

Novel polymer-bound oligopeptides exhibiting antimicrobial activity have been developed. The oligopeptides are unique amino acid sequences which form amphiphilic helices. 

Helical bundles are conveniently described in terms of the heptad repeat pattern (a, b, c, d, e,/,g) , Fig. 5.2, according to which the a and d positions form one side of the folded helix, as do the h and e positions and the g and c positions. Helical bundles are formed from amphiphilic helices and the a and the d positions are... 

Membrane proteins often contain a-helical sections. We have developed a method called oriented circular dichroism (OCD see reference 1), which can be used to determine the orientation of a-helices with respect to the plane of the membrane. This method is simple and easy to use compared with, for example, the NMR method, which requires isotope labeled samples. Indeed, it is the ease of this method that allowed us to examine alamethicin in many different chemical conditions and that resolved a controversial question about the nonconducting state of alamethicin and subsequently led to the discovery of a new phenomenon of amphiphilic helical peptides (2). 

Apolipoprotein A-1 is made up of repeating amphiphilic helices, and a heptad repeat pattern similar to that seen for coUed-coil proteins. However, in aqueous buffer at neutral pH the protein has a random coil stmcture. At pH 3, there is a gain in structure, as the internal fiuorescence shows the three Trp residues are in a hydrophobic pocket (Andreola et al. 2003). CD studies show an acquisition of helical structure at lower pH. The protein is not, however, stable at pH 4, forming insoluble material after around 5 min, the process being one of intermolecular association and then precipitation. Andreola et al. (2003) have hypothesised that the formation of these amyloid aggregates requires the peptide to pass from... 

Butler, S.L. and Falke, J.J. (1998). Cysteine and disulfide scanning reveals two amphiphilic helices in the linker region of the aspartate chemoreceptor. Biochemistry 37, 10 746-10 756. 

Studies on synthetic oligomers performed by Aisenbrey et al. provided information on the interaction of N-labelled amphiphilic helices with oriented lipid membranes and revealed the antimicrobial nature of these oligomers. Solid-state NMR helped to characterize the structure, dynamics and membrane topology of antimicrobial polypeptides such as alamethicin or p-hairpin antimicrobials,a novel dendrimeric peptide with antimicrobial potency against Gram-negative bacteria and tachyplesin-1, a disulfide stabilized p-hairpin antimicrobial peptide. 

Huang HW (1995) Elasticity of lipid bilayer intmacting with amphiphilic helical peptides. J Phys n (France) 5 1427-1431... 

Consistent with the plastidial location of monoterpene biosynthesis [8], immunocy to chemical studies with limonene synthase confirmed the localization of this enzyme to the leucoplasts of peppermint oil glands [87]. Plastid targeting requires the translation of a preprotein bearing an N-terminal transit peptide that directs the newly synthesized enzyme to the plastid for proteolytic processing to the mature form [88]. The limonene synthase cDNA encodes such a preprotein, with an N-terminal sequence that exhibits the typical properties of a transit peptide (rich in serine and threonine (25-30%), rich in small hydrophobic amino acids with few acidic residues, and a propensity to form amphiphilic helices [89,90]). A precise cleavage site between the transit peptide and mature protein is not obvious in the limonene synthase preprotein, and mass spectral... 

A foldamer-based molecular recognition system that has enantiomeric M and P helical conformation was also studied. The diastereoselective complexation of an achiral, amphiphilic, helical m-phenylene ethynylene dodecamer 13 with a chiral plant natural product a-pinene 14 was demonstrated by ICD studies (Figure 10). The stoichiometry of the complex was determined as 1 1 by CD titration measurements based on the linearity of a Benesi-Hildebrand plot and the slope of a Hill plot. The association constant was estimated to be = 6.83 x 10" indicating that 13 can capture 14 efficiently. The results suggested that the chiral guest can stabilize one of the oligomer s enantiomeric helical M or P conformations. 

In both membrane cnrvature sensing and indncing by facial amphiphilic helices, the mechaiusm has to do with incorporation of the heUx into the bilayer. In the case of membrane curvature sensing incorporation is driven by alleviating the membrane stress, present in curved membranes. In the case of membrane curvature inducing proteins a facial amphiphilic alpha helix is forced into the bilayer, for example, binding of a protein domain to the phospholipids, which results in bilayer curving. 

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