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Peptides Capable (peptide + capable)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Templated assembly of the pH-sensitive membrane-lytic peptide GALA

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2004
D.H. Haas
Abstract:, Delivery of protein or nucleic acid therapeutics into intracellular compartments may require facilitation to allow these macromolecules to cross otherwise impermeant cellular membranes. Peptides capable of forming membrane-spanning channels hold promise as just such facilitators, although the requirement for peptide oligomerization to form these channels may limit their effectiveness. Synthetic molecules containing multiple copies of membrane-active peptides attached to a template molecule in a pre-oligomerized form have attracted interest for drug-delivery applications. Using three template designs, we synthesized multimeric versions of the pH-sensitive lytic peptide GALA and compared their performance to monomeric GALA. Template assembly stabilized helix formation: templated GALA retained , -helical structure even at neutral pH, unlike monomeric GALA. In membrane leakage assays, templated GALA retained the pH sensitivity of the monomer, with improved leakage for dimeric GALA. Surprisingly, trimeric GALA was less effective, particularly when synthesized with a larger and more flexible spacer. Surface plasmon resonance analysis indicated that reversible binding of templated GALA to lipid surfaces at acidic conditions was greatly reduced compared with monomeric GALA, but that the amount of irreversibly bound material was similar. We interpreted these results to indicate that templated peptides may cyclize into ,self-satisfied' oligomeric structures, incapable of further aggregation and subsequent pore formation. Future design of templated peptides must be carefully performed to avoid this unwanted consequence. [source]

Identification of a prostate-specific membrane antigen-derived peptide capable of eliciting both cellular and humoral immune responses in HLA-A24+ prostate cancer patients

CANCER SCIENCE, Issue 7 2003
Kazuhiko Kobayashi
We tried to identify prostate-specific membrane antigen (PSMA)-derived peptides capable of eliciting both cellular and humoral immune responses in peripheral blood mononuclear cells (PBMCs) and plasma of HLA-A24+ prostate cancer patients, respectively. For cellular response, peptide-specific and prostate cancer-reactive responses of in vitro -stimulated PBMCs were examined with regard to interferon (IFN)-, production and cytotoxicity against both a parental HLA-A24, prostate cancer cell line (PC-93) and an HLA-A24-expressing transfectant cell line (PC93-A24). For humoral response, patients' plasma was tested for reactivity to the peptides by means of an enzyme-linked immunosorbent assay (ELISA). Among 13 PSMA peptides, PSMA 624,632 peptide induced peptide-specific and tumor-reactive cytotoxic T lymphocytes (CTLs) most effectively. The PSMA 624,632 peptide-stimulated PBMCs from either healthy donors or prostate cancer patients produced a significant level of IFN-, in response to prostate cancer cells in an HLA-A24-restricted manner, and also showed a higher level of cytotoxicity against PC93-A24 than against PC93. Antibodies to the PSMA 624,632 peptide, but not to any others, were detected in prostate cancer patients. These results demonstrate that the PSMA 624,632 peptide could be an appropriate molecule for use in specific immunotherapy of HLA-A24+ patients with prostate cancer. [source]

Peptide-induced suppression of collagen-induced arthritis in HLA,DR1 transgenic mice

ARTHRITIS & RHEUMATISM, Issue 12 2002
Linda K. Myers
Objective To identify peptides capable of altering the immune response to type II collagen (CII) in the context of HLA,DR. Methods Immunizing mice transgenic for the human HLA,DRB1*0101 immune response gene with CII elicits an arthritis (collagen-induced arthritis [CIA]) that resembles rheumatoid arthritis. We have previously identified an immunodominant determinant of CII, CII (263,270), recognized by T cells in the context of DR1. To produce synthetic peptides with the potential of disrupting the DR1-restricted immune response, synthetic analog peptides were developed that contain site-directed substitutions in critical positions. These peptides were used to treat CIA in DR1 transgenic mice. Results An analog peptide, CII (256,276, N263, D266), that inhibited T cell responses in vitro, was identified. When DR1 mice were coimmunized with CII and CII (256,276, N263, D266), the incidence and severity of arthritis were greatly reduced, as was the antibody response to CII. Moreover, CII (256,276, N263, D266) was effective in down-regulating the immune responses to CII and arthritis, even when administered 2 weeks following immunization with CII. Spleen and lymph node cells from CII-immunized mice cultured with CII (256,276, N263, D266) in vitro produced increased amounts of interleukin-4 (IL-4) compared with cells cultured with the wild-type peptide, CII (256,276). Furthermore, CII (256,276, N263, D266) was incapable of preventing arthritis in DR1 IL-4,/, mice (genetically deficient in IL-4). Conclusion These data establish that CII (256,276, N263, D266) is a potent suppressor of the DR-mediated immune response to CII. Its effect is mediated, at least in part, by IL-4. These experiments represent the first description of an analog peptide of CII recognized by T cells in the context of a human major histocompatibility complex molecule that can suppress autoimmune arthritis. [source]

Identification of a prostate-specific membrane antigen-derived peptide capable of eliciting both cellular and humoral immune responses in HLA-A24+ prostate cancer patients

Self-Organisation in the Assembly of Gels from Mixtures of Different Dendritic Peptide Building Blocks

CHEMISTRY - A EUROPEAN JOURNAL, Issue 8 2007
Andrew
Abstract This paper investigates dendritic peptides capable of assembling into nanostructured gels, and explores the effect on self-assembly of mixing different molecular building blocks. Thermal measurements, small angle X-ray scattering (SAXS) and circular dichroism (CD) spectroscopy are used to probe these materials on macroscopic, nanoscopic and molecular length scales. The results from these investigations demonstrate that in this case, systems with different "size" and "chirality" factors can self-organise, whilst systems with different "shape" factors cannot. The "size" and "chirality" factors are directly connected with the molecular information programmed into the dendritic peptides, whilst the shape factor depends on the group linking these peptides together,this is consistent with molecular recognition hydrogen bond pathways between the peptidic building blocks controlling the ability of these systems to self-recognise. These results demonstrate that mixtures of relatively complex peptides, with only subtle differences on the molecular scale, can self-organise into nanoscale structures, an important step in the spontaneous assembly of ordered systems from complex mixtures. [source]