Scope and Applications of Amphiphilic Alkyl‐ and Lipopeptides

Cavalli, Silvia; Kros, Alexander

doi:10.1002/adma.200701914

Cited by 31 publications

(21 citation statements)

References 26 publications

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“…4a) formed hollow tubules or helical ribbons spontaneously; these self-assembled structures protected compound 3 from trypsin degradation [65]. Several reviews describing selfassembly mechanisms, compositions and applications of lipidated peptides were available [84,[101][102][103][104]. Herein, we briefly describe the effects of lipid anchor position and the chain length of fatty acids on the self-assembly and aggregation properties of lipidated peptide.…”

Section: Oligomers and Self-assembling Macromoleculesmentioning

confidence: 99%

Converting Peptides into Drug Leads by Lipidation

Zhang¹,

Bułaj²

2012

CMC

175

139

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Ulceration in the gastrointestinal (GI) mucosa is a common disorder in humans. It has been shown that cigarette smoking is closely related to the increase of peptic ulcer and also plays an inhibitory role on ulcer healing. However, the underlying mechanisms by which cigarette smoke exerts these adverse effects remain largely unknown. It is perhaps partly due to the complexity of chemical compositions in the smoke and furthermore their pathological actions are largely undefined. In this review, we have highlighted the potential adverse effects of the toxic chemical components in cigarette smoke and summarized their possible mechanisms of actions on ulcer formation and healing in the GI tract. We also discuss in detail how cigarette smoke disturbs cell proliferation, influences mucus synthesis and secretion, delays blood vessel formation, and interferes the innate immune responses during ulceration and repair in the GI mucosa.

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Section: Oligomers and Self-assembling Macromoleculesmentioning

confidence: 99%

Converting Peptides into Drug Leads by Lipidation

Zhang¹,

Bułaj²

2012

CMC

175

139

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“…Different aqueous solubilities of the peptide and lipid blocks promote segregation of the latter, leading to formation of supra-molecular structures19, 20. Peptides with various functionalities are thus presented on the surface of colloidal aggregates21, fibrous meshes16, 22 or two-dimensional flat surfaces23, 24.…”

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confidence: 99%

Mechanisms of Peptide Amphiphile Internalization by SJSA-1 Cells in Vitro

2009

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Self-assembly of peptide amphiphiles into nanostructures makes them attractive for a variety of applications in drug and peptide delivery. We here report on the interactions of micelles composed of a palmitoylated, pro-apoptotic peptide derived from p53 tumor suppressor protein with a human cancer cell line. Characterization of self-assembly in aqueous buffered solutions revealed formation of elongated rod-like micelles above a critical micelle concentration. Our results however demonstrate that monomers instead of micelles are internalized, a finding which correlates with the dynamic nature of the assemblies and the non-covalent interactions that hold them together. Internalization is shown to occur via adsorption-mediated, energy-dependent pathways, resulting in accumulation of the material in endocytic vesicles. We conclude that palmitoylation of peptides is an efficient way to increase peptide permeability inside SJSA-1 cells and that increased micelle stability would be required for intact micelle internalization.Synthetic peptides derived from human proteins, or identified via powerful new technologies, have emerged as potential therapeutics for various diseases, acting as signals, promoters or inhibitors of cellular functions. Frequently, their site of action is intracellular and therefore they are required to cross cell membranes in order to reach their target. Among the strategies explored in order to attain this goal, the one receiving the most attention is modification with peptide sequences that are able to translocate inside cells, widely referred to as cell penetrating peptides (CPPs) 1, 2 . A variety of different CPPs have been identified, ranging in activity and mechanism of action. An alternative strategy has been the covalent attachment of a hydrophobic tail onto the peptide of interest 3-6 . Borrowed from nature, where cells link hydrophobic moieties onto proteins to efficiently localize them on cellular membranes 7 , this mechanism has proven a simple, yet effective way to transport peptides inside the cell and thus enhance their activity 8, 9 . Peptide amphiphiles or lipopeptides, as the resulting constructs are usually termed, have a higher affinity for lipid bilayers than the parent peptides 9, 10 and are able to insert into the cell membrane by virtue of their hydrophobic tail. Following this first step toward internalization, the subsequent uptake mechanism and the final destination of lipopeptides remain a subject of investigation. Attaching a hydrophobic tail onto a peptide additionally has implication on its biodistribution. Depending on the type of lipid tail, binding to certain biomolecules in vivo can be promoted in order to aid their transport to sites of interest 11 or act as a drug reservoir in the blood 12 . Moreover, lipopeptides exhibit improved stability against As an example of a pro-apoptotic signal we here selected a peptide derived from the binding site of tumor suppressor p53 to the MDM2 protein 26 . The 16-mer peptide from the N-terminus of p53 (p53 [14][15][16...

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“…This spacer enables extension of the oligopeptide component from the surface of the liposomes. The lipidated oligopeptides are anchored spontaneously in the membrane by means of a phospholipid tail, 1,2-dioleoyl-sn-glycero-3phosphatidylethanolamine (DOPE), [9] which mimics the function of the transmembrane domain of SNARE proteins (Figure 1 a).…”

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confidence: 99%