Peptide lipid surfactants

Arima K, Kahinuma A, Tamura G (1968) Surfactin, a crystalline peptide lipid surfactant produced by Bacillus subtilis isolation, characterization and its inhibition of fibrin clot formation. Biochem Biophys Res Commun... 

Murakami et al. studied alternative pyridoxamine-surfactant systems [23]. These authors synthesized hydrophobic pyridoxamine derivatives (30 and 31) and peptide lipid molecules (32-35). Catalyst 30 or 31 and the peptide lipids formed bilayer membranes in water, which showed transamination reactivity in the presence of metal ions such as Cu(ii). It was proposed that the pyridoxamine moiety was placed in the so-called hydrogen-belt domain interposed between the polar surface region and the hydrophobic domain that is composed of double-chain segments within the bilayer assembly. The basic group (such as imidazole) in the peptide lipid molecules could catalyze the proton transfer involved in the transamination reaction. In addition, marked substrate discrimination by these bilayer membrane systems was performed through hydrophobic interactions between substrates and the catalytic site. 

Finally, there are Type IV SAPs, which mimic characteristics of polymeric and lipid surfactant molecules. Type IV SAPs are by nature amphiphilic the leading head group contains at least one hydrophilic amino acid, which is trailed by a sequence of six identical hydrophobic amino acids to create a hydrophobic tail. It is known that both cationic and anionic amphiphiles will self-assemble into mbu-lar stfuctures at neutral pH [57]. First, the peptides assemble into bilayers in order... 

Type IV SAPs mimic the properties of polymeric and lipid surfactant molecules. They are amphiphilic in nature, as the leading head group is composed of at least one hydrophilic amino acid followed by a string of six identical hydrophobic amino acids to form the hydrophobic tail. At neutral pH, both the cationic and anionic amphiphiles self-assemble into tubular morphologies. These peptides first... 

Bruni, R., Taeusch, H.W., and Waring, A.J. Surfactant protein B Lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain. Proc. Natl. Acad. Sci. USA 1991, 88, 7451-7455. 

Gordon, L.M., Lee, K.Y.C., Lipp, M.M., Zasadzinski, J.A., Walther, F.J., Sherman, M. A., and Waring, A.J. Conformational mapping of the N-terminal segment of surfactant protein B in lipid using C-13-enhanced Fourier transform infrared spectroscopy. J. Peptide Res. 

Drugs, alkaloids, mycotoxins, amino acids, flavinoids, heterocyclic compounds, lipids, steroids, organic acids, terpenes, vitamins. Proteins, peptides, surfactants. 

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

Furthermore, Oda et al. pointed out that there are two topologically distinct types of chiral bilayers, as shown in Figure 5.46.165 Helical ribbons (helix A) have cylindrical curvature with an inner face and an outer face and are the precursors of tubules. These are, for example, the same structures that are observed in the diacetylenic lipid systems discussed in Section 4.1. By contrast, twisted ribbons (helix B) have Gaussian saddlelike curvature, with two equally curved faces and a C2 symmetry axis. They are similar to the aldonamide and peptide ribbons discussed in Sections 2 and 3, respectively. The twisted ribbons in the tartrate-gemini surfactant system were found to be stable in water for alkyl chains with 14-16 carbons. Only micelles form... 

Drug A is a large, peptide-like molecule (MW 700 g/mol) and is highly lipophilic and poorly water soluble. It is a BCS Class II drugs. Its oral bioavailability in capsules and conventional tablet formulations is low, yielding practically undetected blood levels. A novel lipid formulation containing a solvent, a high HLB nonionic surfactant, and a fatty acid were developed with sufLcient oral bioavailability for use in the clinic. 

The permeability of two peptides, P-gp substrate and non P-gp substrate, across caco-2 cells in the presence or absence of polysorbate 80 and cremophor EL, commonly used surfactants in pharmaceutical formulations, was investigated. The permeability of the P-gp substrate peptide across caco-2 cells was enhanced in the presence of polysorbate 80 and cremophor EL, whereas the non-P-gp substrate peptide was not affected by these surfactants [94]. Another commonly used lipidic excipient that has been shown to inhibit P-gp mediated efflux is D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) [95]. The insertion of a known CYP3A4 and P-gp inhibitor to the formulation is another approach to elevate bioavailability. 

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). 

Modified and natural lipids and polymeric surfactants are increasingly being used in pharmaceutical formulations to increase the bioavailability of difficult drugs difficult usually because they have very poor solubility in aqueous environments. While these molecules may not themselves be biologically active, what happens to them in the gastrointestinal (GI) tract may influence their intended function, especially if they are acting to protect the active principle, for example, in the case of therapeutic peptides. 

Synthetic surfactants Laureth-9 sodium lauryl sulphate polysorbate 20 and 80 PEG-8 laurate sorbitan laurate glyceryl monolaurate saponins (e.g., Quillaja saponins) membrane interaction extraction of membrane proteins and lipids solubilization of peptides... 

Surfactants Sodium lauryl sulfate Polyoxyethylene oxide-9 ethers Solubilization of proteins/peptides Perturbation of membrane layers Extraction of membrane proteins and lipids... 

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