Peptides, cyclic lipidation

Products of lipid peroxidation Pros taglandins Bacterial filtrate factors N-Formyl methionyl peptides Cyclic purine nucleotides Transfer factor... 

Cyclic peptide nucleus Lipid side chain S. aureus S. epidermidis E. faecdis... 

Many peptide antibiotics have novel structural motifs, such as cyclic structures and are often further modified, (such as in jS-lactamic antibiotics) and conjugated with sugars, lipids, and other molecules. 

A number of polypeptide biomarkers have also been identified in the mass range below 4000,28-31 which are cyclic secondary metabolites bonded to lipids or sugars. These peptide sequences are not directly translated from DNA,32... 

Keywords Amphiphilic peptide-lipid interactions Cyclic fS-sheet structure ... 

Bacitracin (Fig. 4) is a cyclic peptide antibiotic. The lipid II molecule involved in the bacterial cell wall biosynthesis has a C55 isoprenyl pyrophosphate moiety that must be dephosphorylated so that it can reparticipate in another round of lipid II transfer. Bacitracin binds to the isoprenyl pyrophosphate and prevents the dephosphorylation which, in turn, blocks cell wall growth by interfering with the release of the muropeptide subunits to the outside of the bacterial cell membrane. Bacitracin inhibits similar reactions in eukaryotic cells. So, it is systemically toxic but is an effective and widely used topical antibiotic. 

Fig. 3. (a) Chemical structure of a synthetic cyclic peptide composed of an alternating sequence of D- and L-amino acids. The side chains of the amino acids have been chosen such that the peripheral functional groups of the flat rings are hydrophobic and allow insertion into lipid bilayers, (b) Proposed structure of a self-assembled transmembrane pore comprised of hydrogen bonded cyclic peptides. The channel is stabilized by hydrogen bonds between the peptide backbones of the individual molecules. These synthetic pores have been demonstrated to form ion channels in lipid bilayers (71). 

A few years ago, we began a research program to develop methods of analysis which would involve the use of FAB and a high performance tandem mass spectrometer. The tandem instrument was the first triple sector mass spectrometer to be designed and built by a commercial instrument company (Kratos of Manchester, U.K.). The first mass spectrometer of the combination is a double focussing Kratos MS-50 which is coupled to a low resolution electrostatic analyzer, which serves as the second mass spectrometer U). This FAB MS-MS combination has been used to verify the structures of an unknown cyclic peptide (2), a new amino acid modified by diphtheria toxin (3), and an ornithine-containing lipid (4). A number of methods have also been worked out which rely on this instrumentation. They Include the structural determination of cyclic peptides (5), nucleosides and nucleotides (6), and unsaturated fatty acids (7) and the analysis of mixtures of both anionic (8) and cationic surfactants (9). 

In the larger peptide antibiotic compounds comprising the class of lantibiotics, the shape of the molecule is determined by several cyclic peptides, including two annulated peptide rings, present within one molecule, giving the lantibiotic a unique way to interact with the target molecule lipid II and subsequent pore-forming capabilities in phospholipid membranes [2]. 

As schematically own in Fig. 30, the cell membranes of living organism (/ S6) are composed of a lipid bilayer and form the interface between the intracellular and the extracellular aqueous parts. Concentrations of metal ions and amino adds in the cell are thus kept constant and the biological functions in the cell are executed. Specifically, the concentration of metal ions is in a dynamic equilibrium between the inside and the outside of the cell membrane, and it has been suggested that the mass tran rt through the membrane is mediated by lipoproteins. For the metal-km tran rt through the membrane, the participation of a group of cyclic conqxrunds called lonophores is important, which is dosely related to the antibiotic actions of cyclic peptides and cyclic depsipeptides (iJ6). These cyclic compounds are compatibile... 

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