Design of a short membrane-destabilizing peptide covalently bound to liposomes

Puyal, Christophe; Maurin, Luc; Miquel, Geneviève; Bienvenüe, Alain; Philippot, Jean R.

doi:10.1016/0005-2736(94)90265-8

Cited by 37 publications

(30 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only in the presence of liposomes did the 222 nm well minima become more pronounced at pH 5. These trends of SFP3 are consistent with studies of the parent peptide GALA in presence of lipids (41) and with its sister peptide SFP1 in aqueous solution without lipids (40).…”

Section: Peptide Structuresupporting

confidence: 86%

“…INF7 is the first 23 amino acids of the amino-terminal sequence of influenza virus X-31 (H3N2) hemagglutinin subunit HA-2 with two G to E substitutions (positions 4 and 7) that render the peptide more membrane-active in in vitro assays (28). The other peptide is a 15-mer known as short fusion peptide 3 (SFP3) (40). This amphipathic peptide is a shortened version of the synthetic pH-sensitive peptide GALA (41), which has been described in detail for its membrane activity in vitro (20).…”

Section: In Vitro Characterization Of Peptidesmentioning

confidence: 99%

See 1 more Smart Citation

pH-Dependent Lytic Peptides Discovered by Phage Display

Hirosue

Weber

2006

Biochemistry

View full text Add to dashboard Cite

Lipid membranes compartmentalize eukaryotic cells and separate the cell interior from the extracellular milieu. So far, studies of peptide and protein interactions with membranes have largely been limited to naturally occurring peptides or to sequences designed on the basis of structural information and biophysical parameters. To expand on these studies, utilizing a system with minimal assumptions, we used phage-display technology to identify 12 amino-acid-long peptides that bind to liposomes at pH 5.0 but not at pH 7.5. Of the nineteen peptides discovered three were able to cause leakage of liposome contents. Multivalent presentation of these membrane-active peptides by conjugation onto poly(L-Lysine) enhanced their lytic potential. Secondary structures were analyzed by circular dichroism in aqueous 2,2,2-trifluoroethanol and in buffered aqueous solutions, in both the presence and absence of liposomes. Two of the three lytic peptides show alpha helical profiles whereas none of the non-lytic peptides formed stable secondary structures.The diverse characteristics of the peptides identified in this study demonstrate that phage-displayed peptide library screens on lipid membranes result in the discovery of non-classical membrane-active peptides, whose study will provide novel insights into peptide-membrane interactions.Membranes play an integral role in biology by acting as compartmentalizing barriers and are involved in many biological processes such as signaling (1), membrane trafficking (2) including endo-and exocytosis (3), and viral cell entry and propagation (4).Much of our understanding of protein-membrane interactions has been gained from studying the interaction of viral fusion proteins with membranes (5). The study of the interaction of fusion peptides of enveloped viruses with membranes proved to be particularly fruitful (6). The knowledge gained by these studies has greatly increased our understanding of not only the role of these fusion peptides in membrane fusion but yielded important insights into the interaction of peptides with membranes in general. Furthermore, these studies allowed for the harnessing peptides for improved delivery of genetic material and membrane impermeable drugs into the cell cytoplasm (7).Despite the large number of membrane-active peptides known, no apparent consensus sequence or motif exists that governs membrane activity (8). Mechanistically, membrane disturbance can range from surface or interfacial effects such as the "carpet" model (9,10) membrane insertion (11), membrane fusion, pore formation, or membrane rupture. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of these mechanisms the structure and length requirements may be different. Until now, regions of both cellular and viral proteins as well as peptides that interact with membranes have been discovered predominantly by deletion and substitution studies (12), by homology (13), by photolabeling studies (14) and by biophysical analyses (15-17).A more encompassing approach is an exp...

show abstract

Section: Peptide Structuresupporting

confidence: 86%

Section: In Vitro Characterization Of Peptidesmentioning

confidence: 99%

pH-Dependent Lytic Peptides Discovered by Phage Display

Hirosue

Weber

2006

Biochemistry

View full text Add to dashboard Cite

show abstract

“…Similarly, linear variations were noted for all other ionophores studied, but the slope and the exclusion surface pressure ⌸ e (which corresponds to ⌬⌸ ϭ 0) differed for the various ionophores (see Table 1). As commonly observed in such penetration experiments (20), the ⌬⌸ values decreased when the packing density in the phospholipid layer increased, and extrapolation of the curve to zero increase in surface pressure indicated the value of the exclusion surface pressure ⌸ e above which interactions no longer occurred. Here the ⌸ e values were higher than 43 mN/m for all ionophores under study.…”

Section: Ionophore Penetration Into Egg Pc Monolayersmentioning

confidence: 83%

Ionophore–Phospholipid Interactions in Langmuir Films in Relation to Ionophore Selectivity toward Plasmodium-Infected Erythrocytes

Gumila

Miquel²,

Seta

et al. 1999

Journal of Colloid and Interface Science

Self Cite

View full text Add to dashboard Cite

“…We have utilized encapsulation of diINF-7 as a means to guarantee delivery of sufficient quantities of peptides into the endosomal compartment, which is required for effective destabilization of liposomal as well as endosomal membranes with subsequent cytosolic drug release. The possibility to attach the fusogenic peptide to the liposome membrane has been explored by us 2 and several other groups (38,(43)(44)(45). However, the general conclusion is that lipid modification of fusogenic peptides leads to an altered conformation of the peptides, thereby influencing their fusogenic behavior (38,45).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of an Endosome-disruptive Peptide and Its Application in Cytosolic Delivery of Immunoliposome-entrapped Proteins

Mastrobattista

Koning

Bloois

et al. 2002

Journal of Biological Chemistry

167

View full text Add to dashboard Cite

Antibody-directed liposomes (immunoliposomes) are frequently used for targeted drug delivery. However, delivery of large biotherapeutic molecules (i.e. peptides, proteins, or nucleic acids) with immunoliposomes is often hampered by an inefficient cytosolic release of entrapped macromolecules after target cell binding and subsequent endocytosis of immunoliposomes. To enhance cytosolic drug delivery from immunoliposomes present inside endosomes, a pH-dependent fusogenic peptide (diINF-7) resembling the NH 2 -terminal domain of influenza virus hemagglutinin HA-2 subunit was used. Functional characterization of this dimeric peptide showed its ability to induce fusion between liposome membranes and leakage of liposome-entrapped compounds when exposed to low pH. In a second series of experiments, diINF-7 peptides were encapsulated in immunoliposomes to enhance the endosomal escape of diphtheria toxin A chain (DTA), which inhibits protein synthesis when delivered into the cytosol of target cells. Immunoliposomes targeted to the internalizing epidermal growth factor receptor on the surface of ovarian carcinoma cells (OVCAR-3) and containing encapsulated DTA did not show any cytotoxicity toward OVCAR-3 cells. Cytotoxicity was only observed when diINF-7 peptides and DTA were co-encapsulated in the immunoliposomes. Thus, diINF-7 peptides entrapped inside liposomes can greatly enhance cytosolic delivery of liposomal macromolecules by pH-dependent destabilization of endosomal membranes after cellular uptake of liposomes.To exert an optimal therapeutic effect, an administered drug must safely reach not only its target cell but also the appropriate location within that cell. Many biotherapeutic agents (e.g. peptides, proteins, and nucleic acids) act at sites in the cytosol or nucleus that are difficult to reach due to poor membrane permeation characteristics. Therefore, these biotherapeutic agents rely on drug carriers that allow cytosolic delivery of these agents into diseased cells.One attractive strategy to obtain cytosolic delivery is the development of fusion-competent antibody-directed liposomes (immunoliposomes) that, after receptor binding, can fuse with the plasma-membrane of target cells or, after endocytosis of liposomes, with the endosomal membranes. This membrane fusion process should result in cytosolic access of liposomeentrapped drug molecules. Such fusion-competent liposomes can be obtained by disassembling enveloped viruses, isolating their fusion-promoting components, and reassembling these into vesicles to obtain so-called virosomes (1-4). Another, more refined approach involves the use of synthetic peptides designed to resemble the putative fusion peptide of viruses (5-8).It is hypothesized that destabilization of endosomal membranes is less damaging than plasma membrane destabilization. The latter may result in cytotoxicity through eradication of the electrochemical potential generated by the asymmetric distribution of ions across the plasma membrane. Therefore, drug delivery into the cytosol of target ce...

show abstract

Design of a short membrane-destabilizing peptide covalently bound to liposomes

Cited by 37 publications

References 41 publications

pH-Dependent Lytic Peptides Discovered by Phage Display

pH-Dependent Lytic Peptides Discovered by Phage Display

Ionophore–Phospholipid Interactions in Langmuir Films in Relation to Ionophore Selectivity toward Plasmodium-Infected Erythrocytes

Functional Characterization of an Endosome-disruptive Peptide and Its Application in Cytosolic Delivery of Immunoliposome-entrapped Proteins

Contact Info

Product

Resources

About