LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 120

Search options

  1. Article ; Online: Synthetic Molecular Evolution of Cell Penetrating Peptides.

    Wimley, William C

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2383, Page(s) 73–89

    Abstract: Rational design and optimization of cell penetrating peptides (CPPs) is difficult to accomplish because of the lack of quantitative sequence-structure-function rules describing the activity and because of the complex, poorly understood mechanisms of CPPs. ...

    Abstract Rational design and optimization of cell penetrating peptides (CPPs) is difficult to accomplish because of the lack of quantitative sequence-structure-function rules describing the activity and because of the complex, poorly understood mechanisms of CPPs. Synthetic molecular evolution is a powerful method to identify gain-of-function cell penetrating peptide variants in this situation. Synthetic molecular evolution requires the design and synthesis of iterative, knowledge-based peptide libraries and the screening of such libraries in complex orthogonal cell-based screens for improved activity. In this chapter, we describe methods for synthesizing powerful combinatorial peptide libraries for synthetic molecular evolution.
    MeSH term(s) Cell-Penetrating Peptides/genetics ; Evolution, Molecular ; Peptide Library
    Chemical Substances Cell-Penetrating Peptides ; Peptide Library
    Language English
    Publishing date 2021-11-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1752-6_5
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Determining the statistical significance of the difference between arbitrary curves: A spreadsheet method.

    Hristova, Kalina / Wimley, William C

    PloS one

    2023  Volume 18, Issue 10, Page(s) e0289619

    Abstract: We present a simple, spreadsheet-based method to determine the statistical significance of the difference between any two arbitrary curves. This modified Chi-squared method addresses two scenarios: A single measurement at each point with known standard ... ...

    Abstract We present a simple, spreadsheet-based method to determine the statistical significance of the difference between any two arbitrary curves. This modified Chi-squared method addresses two scenarios: A single measurement at each point with known standard deviation, or multiple measurements at each point averaged to produce a mean and standard error. The method includes an essential correction for the deviation from normality in measurements with small sample size, which are typical in biomedical sciences. Statistical significance is determined without regard to the functionality of the curves, or the signs of the differences. Numerical simulations are used to validate the procedure. Example experimental data are used to demonstrate its application. An Excel spreadsheet is provided for performing the calculations for either scenario.
    MeSH term(s) Data Collection ; Sample Size
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0289619
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Cytosolic Delivery of Bioactive Cyclic Peptide Cargo by Spontaneous Membrane Translocating Peptides.

    Ferrie, Ryan P / Fuselier, Taylor / Wimley, William C

    ACS omega

    2024  Volume 9, Issue 7, Page(s) 8179–8187

    Abstract: Cyclic peptides that inhibit protein-protein interactions have significant advantages over linear peptides and small molecules for modulating cellular signaling networks in cancer and other diseases. However, the permeability barrier of the plasma ... ...

    Abstract Cyclic peptides that inhibit protein-protein interactions have significant advantages over linear peptides and small molecules for modulating cellular signaling networks in cancer and other diseases. However, the permeability barrier of the plasma membrane remains a formidable obstacle to the development of cyclic peptides into applicable drugs. Here, we test the ability of a family of synthetically evolved spontaneous membrane translocating peptides (SMTPs) to deliver phalloidin, a representative bioactive cyclic peptide, to the cytosol of human cells in culture. Phalloidin does not enter cells spontaneously, but if delivered to the cytosol, it inhibits actin depolymerization. We thus use a wound-healing cell mobility assay to assess the biological activity of phalloidin conjugated to three SMTPs that we previously discovered. All three SMTPs can deliver phalloidin to the cell cytosol, and one does so at concentrations as low as 3 μM. Delivery occurs despite the fact that the SMTPs were originally selected based on membrane translocation with no cargo other than a small fluorescent dye. These results show that SMTPs are viable delivery vehicles for cyclic peptides, although their efficiency is moderate. Further, these results suggest that one additional generation of synthetic molecular evolution could be used to optimize SMTPs for the efficient delivery of any bioactive cyclic peptide into cells.
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.3c08701
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: How We Came to Understand the "Tumultuous Chemical Heterogeneity" of the Lipid Bilayer Membrane.

    Wimley, William C

    The Journal of membrane biology

    2020  Volume 253, Issue 3, Page(s) 185–190

    Abstract: The path to our modern understanding of the structure of the lipid bilayer membrane is a long one that can be traced from today perhaps as far back as Benjamin Franklin in the eighteenth century. Here, I provide a personal account of one of the important ...

    Abstract The path to our modern understanding of the structure of the lipid bilayer membrane is a long one that can be traced from today perhaps as far back as Benjamin Franklin in the eighteenth century. Here, I provide a personal account of one of the important steps in that path, the description of the "Complete Structure" of a hydrated, fluid phase dioleoyl phosphatidylcholine bilayer by the joint refinement of neutron and X-ray diffraction data by Stephen White and his colleagues.
    MeSH term(s) Chemical Phenomena ; Lipid Bilayers/chemistry ; Models, Molecular ; Molecular Conformation ; Molecular Structure ; Phosphatidylcholines/chemistry ; Structure-Activity Relationship ; X-Ray Diffraction
    Chemical Substances Lipid Bilayers ; Phosphatidylcholines ; 1,2-oleoylphosphatidylcholine (EDS2L3ODLV)
    Language English
    Publishing date 2020-06-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 3082-x
    ISSN 1432-1424 ; 0022-2631
    ISSN (online) 1432-1424
    ISSN 0022-2631
    DOI 10.1007/s00232-020-00126-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 613: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: Application of Synthetic Molecular Evolution to the Discovery of Antimicrobial Peptides.

    Wimley, William C

    Advances in experimental medicine and biology

    2019  Volume 1117, Page(s) 241–255

    Abstract: Despite long-standing promise and many known examples, antimicrobial peptides (AMPs) have failed, with few exceptions, to significantly impact human medicine. Impediments to the systemic activity of AMPs include proteolysis, host cell interactions, and ... ...

    Abstract Despite long-standing promise and many known examples, antimicrobial peptides (AMPs) have failed, with few exceptions, to significantly impact human medicine. Impediments to the systemic activity of AMPs include proteolysis, host cell interactions, and serum protein binding, factors that are not often considered in the early stages of AMP development. Here we discuss how synthetic molecular evolution, iterative cycles of library design, and physiologically relevant screening can be used to evolve AMPs that do not have these impediments.
    MeSH term(s) Antimicrobial Cationic Peptides/chemistry ; Directed Molecular Evolution ; Humans ; Protein Engineering
    Chemical Substances Antimicrobial Cationic Peptides
    Language English
    Publishing date 2019-04-12
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-13-3588-4_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: How Does Melittin Permeabilize Membranes?

    Wimley, William C

    Biophysical journal

    2018  Volume 114, Issue 2, Page(s) 251–253

    MeSH term(s) Escherichia coli ; Melitten ; Membranes
    Chemical Substances Melitten (20449-79-0)
    Language English
    Publishing date 2018-01-31
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2017.11.3738
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 235: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 2: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article: The Mechanism of Membrane Permeabilization by Peptides: Still an Enigma.

    Wimley, William C / Hristova, Kalina

    Australian journal of chemistry

    2019  Volume 73, Issue 3, Page(s) 96–103

    Abstract: Peptide-induced permeabilization of lipid vesicles has been measured for decades and has provided many insights into the sequence-structure-function relationships of membrane-active peptides. However, researchers in the field have noted that many ... ...

    Abstract Peptide-induced permeabilization of lipid vesicles has been measured for decades and has provided many insights into the sequence-structure-function relationships of membrane-active peptides. However, researchers in the field have noted that many experiments show transient permeabilization, in which a burst of leakage occurs immediately after peptide addition, followed by a slowdown or cessation of leakage before all contents have been released. This widely observed, but rarely studied, phenomenon is not explained by standard equilibrium pore models that are commonly invoked in both experimental and computational studies. Here we discuss observations of transient permeabilization, and we outline a pathway towards understanding this enigmatic phenomenon.
    Language English
    Publishing date 2019-11-11
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 1472214-8
    ISSN 0004-9425 ; 0365-3676
    ISSN 0004-9425 ; 0365-3676
    DOI 10.1071/CH19449
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Membrane-selective nanoscale pores in liposomes by a synthetically evolved peptide: implications for triggered release.

    Sun, Leisheng / Hristova, Kalina / Wimley, William C

    Nanoscale

    2021  Volume 13, Issue 28, Page(s) 12185–12197

    Abstract: Peptides that form nanoscale pores in lipid bilayers have potential applications in triggered release, but only if their selectivity for target synthetic membranes over bystander biomembranes can be optimized. Previously, we identified a novel family of ... ...

    Abstract Peptides that form nanoscale pores in lipid bilayers have potential applications in triggered release, but only if their selectivity for target synthetic membranes over bystander biomembranes can be optimized. Previously, we identified a novel family of α-helical pore-forming peptides called "macrolittins", which release macromolecular cargoes from phosphatidylcholine (PC) liposomes at concentrations as low as 1 peptide per 1000 lipids. In this work, we show that macrolittins have no measurable cytolytic activity against multiple human cell types even at high peptide concentration. This unprecedented selectivity for PC liposomes over cell plasma membranes is explained, in part, by the sensitivity of macrolittin activity to physical chemical properties of the bilayer hydrocarbon core. In the presence of cells, macrolittins release all vesicle-entrapped cargoes (proteins and small molecule drugs) which are then readily uptaken by cells. Triggered release occurs without any direct effect of the peptide on the cells, and without vesicle-vesicle or vesicle-cell interactions.
    MeSH term(s) Cell Membrane ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers ; Liposomes ; Peptides
    Chemical Substances Lipid Bilayers ; Liposomes ; Peptides
    Language English
    Publishing date 2021-06-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2515664-0
    ISSN 2040-3372 ; 2040-3364
    ISSN (online) 2040-3372
    ISSN 2040-3364
    DOI 10.1039/d1nr03084a
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Determining the Effects of Membrane-Interacting Peptides on Membrane Integrity.

    Wimley, William C

    Methods in molecular biology (Clifton, N.J.)

    2015  Volume 1324, Page(s) 89–106

    Abstract: In the study of cell-penetrating and membrane-translocating peptides, a fundamental question occurs as to the contribution arising from fundamental peptide-membrane interactions, relative to the contribution arising from the biology and energy of the ... ...

    Abstract In the study of cell-penetrating and membrane-translocating peptides, a fundamental question occurs as to the contribution arising from fundamental peptide-membrane interactions, relative to the contribution arising from the biology and energy of the cell, mostly occurring in the form of endocytosis and subsequent events. A commonly used approach to begin addressing these mechanistic questions is to measure the degree to which peptides can interact with, and physically disrupt, the integrity of synthetic lipid bilayers. Here, we describe a set of experimental methods that can be used to measure the potency, kinetics, transience, and the effective size of peptide-induced membrane disruption.
    MeSH term(s) Animals ; Cell Membrane/chemistry ; Cell Membrane/metabolism ; Cell Membrane Permeability ; Cell-Penetrating Peptides/chemistry ; Cell-Penetrating Peptides/metabolism ; Dextrans/analysis ; Dextrans/metabolism ; Fluorescent Dyes/analysis ; Fluorescent Dyes/metabolism ; Fluorometry/methods ; Humans ; Lipid Bilayers/chemistry ; Lipid Bilayers/metabolism ; Naphthalenes/analysis ; Naphthalenes/metabolism ; Terbium/analysis ; Terbium/metabolism ; Unilamellar Liposomes/chemistry ; Unilamellar Liposomes/metabolism
    Chemical Substances Cell-Penetrating Peptides ; Dextrans ; Fluorescent Dyes ; Lipid Bilayers ; Naphthalenes ; Unilamellar Liposomes ; Terbium (06SSF7P179) ; 8-amino-1,3,6-naphthalenetrisulfonic acid (D33V8NB7KB)
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-2806-4_6
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  10. Article ; Online: pH-triggered pore-forming peptides with strong composition-dependent membrane selectivity.

    Kim, Sarah Y / Bondar, Ana-Nicoleta / Wimley, William C / Hristova, Kalina

    Biophysical journal

    2021  Volume 120, Issue 4, Page(s) 618–630

    Abstract: Peptides that self-assemble into nanometer-sized pores in lipid bilayers could have utility in a variety of biotechnological and clinical applications if we can understand their physical chemical properties and learn to control their membrane selectivity. ...

    Abstract Peptides that self-assemble into nanometer-sized pores in lipid bilayers could have utility in a variety of biotechnological and clinical applications if we can understand their physical chemical properties and learn to control their membrane selectivity. To empower such control, we have used synthetic molecular evolution to identify the pH-dependent delivery peptides, a family of peptides that assemble into macromolecule-sized pores in membranes at low peptide concentration but only at pH < ∼6. Further advancements will also require better selectivity for specific membranes. Here, we determine the effect of anionic headgroups and bilayer thickness on the mechanism of action of the pH-dependent delivery peptides by measuring binding, secondary structure, and macromolecular poration. The peptide pHD15 partitions and folds equally well into zwitterionic and anionic membranes but is less potent at pore formation in phosphatidylserine-containing membranes. The peptide also binds and folds similarly in membranes of various thicknesses, but its ability to release macromolecules changes dramatically. It causes potent macromolecular poration in vesicles made from phosphatidylcholine with 14 carbon acyl chains, but macromolecular poration decreases sharply with increasing bilayer thickness and does not occur at any peptide concentration in fluid bilayers made from phosphatidylcholine lipids with 20-carbon acyl chains. The effects of headgroup and bilayer thickness on macromolecular poration cannot be accounted for by the amount of peptide bound but instead reflect an inherent selectivity of the peptide for inserting into the membrane-spanning pore state. Molecular dynamics simulations suggest that the effect of thickness is due to hydrophobic match/mismatch between the membrane-spanning peptide and the bilayer hydrocarbon. This remarkable degree of selectivity based on headgroup and especially bilayer thickness is unusual and suggests ways that pore-forming peptides with exquisite selectivity for specific membranes can be designed or evolved.
    MeSH term(s) Hydrogen-Ion Concentration ; Lipid Bilayers ; Molecular Dynamics Simulation ; Peptides ; Protein Structure, Secondary
    Chemical Substances Lipid Bilayers ; Peptides
    Language English
    Publishing date 2021-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2021.01.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 235: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 2: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top