Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Germany  (12)
  • SECONDARY STRUCTURE  (5)
Collection
Keywords
  • 1
    Keywords: PEPTIDE ; SIMULATIONS ; SPECTRA ; Germany ; PROTEINS ; DYNAMICS ; SIMULATION ; PARAMETERS ; VACCINE ; KINETICS ; ALPHA-HELIX ; CD4-BINDING DOMAIN ; CONFORMATIONAL SWITCH ; EXPLICIT SOLVENT WATER ; GP120 ; IMMUNOGENIC PEPTIDE ; molecular dynamics simulation,peptide,convergence ; MOLECULAR-DYNAMICS SIMULATION ; TRIFLUOROETHANOL
    Abstract: To examine the conformational properties in aqueous solution of a 15-residue peptide that is a potential pharmacophore for AIDS vaccine development, molecular dynamics simulations were performed in water starting from structures determined experimentally in three different organic solvents. Convergence characteristics of the simulation are examined in Cartesian and conformational spaces. In addition, novel analysis tools are employed including a multidimensional scaling method to represent the distance between trajectory frames. As these methods are based on a variety of physical parameters, they provide a useful cross-check on the structural convergence. Theoretical two-dimensional (2D) H-1-NMR spectra are also generated. These are superficially quite different in appearance, demonstrating that backbone similarities difficult to identify by visual inspection of 2D NMR data can be revealed using the methods described here. (C) 2003 Wiley Periodicals, Inc
    Type of Publication: Journal article published
    PubMed ID: 14517902
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: PEPTIDE ; Germany ; COMMON ; INFORMATION ; TOOL ; SITE ; PROTEIN ; PROTEINS ; INDEX ; BINDING ; SEQUENCE ; SEQUENCES ; SIGNAL ; ACID ; GLYCOPROTEIN ; DESIGN ; PEPTIDES ; PARAMETERS ; STABILITY ; BEHAVIOR ; INITIATION ; GP120 ; CHAIN ; PROTEIN DESIGN
    Abstract: Certain sequences within proteins have the ability to undergo an abrupt cooperative conformational switch from beta-strand to helix in response to decreasing polarity of the environment. This behavior was first observed at the CD4 binding site of the envelope glycoprotein gp120 of HIV-1, but evidence has accumulated that polarity-driven beta --〉 alpha switches may be widespread, serving both to facilitate binding on protein/membrane or protein/protein contact and to signal that docking has occurred. The characteristics identified so far that distinguish switch sequences (a reverse turn at the N-terminus that acts as a helix initiation site, a conserved tryptophan residue downstream, and high potential for both the helix and beta-fold) appear to be necessary but not sufficient, as some otherwise promising sequences found in data bank searches proved not to be capable of cooperative refolding. Analysis of existing switches has led to the development of the side chain interaction index (SCII) as a further parameter characterizing the beta --〉 alpha polarity-driven switch. Data bank searches using this additional parameter have successfully identified a series of new potential switch sequences. All of them have in common the amino acid tetrad LPCR at the N-terminus and a tryptophan 5-20 residues C-terminal to it. Those with a high SCII as well, when synthesized and tested, exhibited strongly cooperative polarity-driven refolding. Control peptides, containing all other parameters but with a low SCII, did not. Using this new information, an artificial sequence was designed that had a high SCII as well as the initiation site, conserved tryptophan, and high P-alpha and P-beta. When synthesized and tested, this sequence did in fact behave as a conformational switch, refolding cooperatively from beta-fold to helix at a threshold value of 30% TFE. The successful design of a polarity-driven conformational switch opens the possibility of using this motif as a tool in protein engineering
    Type of Publication: Journal article published
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: PEPTIDE ; Germany ; COMMON ; PROTEIN ; PROTEINS ; DOMAIN ; ANTIGEN ; DYNAMICS ; SIMULATION ; SEQUENCE ; SEQUENCES ; antibodies ; antibody ; TARGET ; DESIGN ; VARIABILITY ; VACCINE ; STRATEGIES ; PREDICTION ; GP120 ; MOLECULAR-DYNAMICS ; HIV-1 ; GENOMIC DIVERSITY ; HTLV-III ; MINIMIZATION
    Abstract: The most promising target antigen for an HIV vaccine designed using the classic antibody strategy has been the viral coat protein gp120. Unfortunately, its high variability has prevented this approach. We examine here a 15-residue peptide derived from the CD4-binding domain of gp120. By use of molecular dynamics computer simulation, it is shown that despite considerable sequence variation, the three-dimensional structure of the peptide is preserved over the full range of clade-specific sequences. Furthermore, sequences threaded onto the structure exhibit common three-dimensional electrostatic and hydrophobic properties. These common physicochemical characteristics constitute a pharmacophoric footprint that promises to be useful in the design of a synthetic antigen for vaccine development
    Type of Publication: Journal article published
    PubMed ID: 15239651
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: PEPTIDE ; CELLS ; GROWTH ; IN-VITRO ; tumor ; BLOOD ; CELL ; Germany ; IN-VIVO ; MODEL ; THERAPY ; VITRO ; VIVO ; imaging ; screening ; cell line ; ACCUMULATION ; LINES ; NUCLEAR-MEDICINE ; TIME ; SERA ; primary ; BINDING ; CELL-LINES ; SEQUENCE ; SEQUENCES ; ACID ; MOUSE ; ASSAY ; CELL-LINE ; LINE ; DISPLAY ; CELLULAR UPTAKE ; PEPTIDES ; BIODISTRIBUTION ; STABILITY ; HEAD ; NECK ; CLEARANCE ; MOUSE MODEL ; KINETICS ; specificity ; SECONDARY STRUCTURE ; cell lines ; nuclear medicine ; AFFINITY ; PHAGE DISPLAY ; SERUM ; targeting ; radiology ; RE ; INCREASE ; LIBRARIES ; LEVEL ; methods ; TUMOR-CELL ; ASSAYS ; INTERNALIZATION ; NUCLEAR ; MCF-7 CELLS ; technique ; pharmacology ; USA ; uptake ; tumor targeting ; in vivo ; MEDICINE ; TOO ; binding affinity ; MODIFIED PEPTIDE ; CONJUGATION ; BINDING PEPTIDE ; BLOOD-LEVELS ; circular dichroism ; peptide structure
    Abstract: The transfer of peptide sequences identified by screening of phage-displayed libraries to clinical application is often difficult. This study investigated whether coupling of a new peptide, FROP-1, to the chelator 1,4,7,10-tetraazacyclododecane-1,4, 7,10-tetraacetic acid (DOTA) resulted in structural restriction and, consequently, improved binding and stability. Methods: The peptide FROP-1 was coupled to the chelator DOTA and labeled with In-111. The structural changes caused by the addition of the chelator were determined by circular dichroism. The properties of this modified peptide were investigated in in vitro binding assays and monitored for kinetics, competition, and internalization as well as serum stability. A cell-type binding profile was established and the in vivo biodistribution was evaluated in a nude mouse model. Results: When compared with the free peptide without chelator, FROPDOTA revealed different cellular uptake kinetics, reaching a maximum at 2 h in vitro. The cells completely accumulated the tracer, and competition experiments revealed that 99.4% (FRO82-2 cells), 98.6% (MCF-7 cells), or 99.3% (average for 3 primary head and neck tumor cell lines) of tracer accumulation could be suppressed, revealing the specificity of this process. The internalization kinetics determined in MCF-7 cells supported this finding: After an incubation time of 180 min, the major fraction of FROPDOTA was trapped intracellularly. Serum stability experiments revealed an increase in stability due to the chelator, with a half-life of 71 min. Circular dichroism measurements indicated a fixed alpha-helix structure of FROPDOTA representing a strong change in secondary structure. In competition binding experiments, the binding constant (K-D) to FRO82-2 cells was determined to be 494 nM. Despite this avid binding affinity, the binding kinetics were found to be too slow to induce an uptake in vivo before clearance. Consequently, the biodistribution revealed a rapid renal and hepatobiliary clearance, with blood levels dropping from 5.48 +/- 0.26 %lD/g (percentage injected dose per gram) 5 min after injection to 0.77 +/- 0.15 %ID/g at 135 min after injection. Conclusion: This study revealed that peptides that are identified by display techniques may be underrated. Careful alteration of their structure will permit going beyond the possibilities that the limited pool of naturally occurring peptides provide for tumor targeting
    Type of Publication: Journal article published
    PubMed ID: 17704241
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: PEPTIDE ; SPECTRA ; Germany ; PROTEIN ; BIOLOGY ; MOLECULAR-BIOLOGY ; FUSION ; PEPTIDES ; SECONDARY STRUCTURE ; molecular biology ; molecular ; CHEMISTRY ; methods ; USA ; SPECTRUM
    Type of Publication: Journal article published
    PubMed ID: 17320030
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: ENERGIES ; PEPTIDE ; Germany ; LINES ; DOMAIN ; IONS ; BINDING ; SEQUENCE ; ACID ; ACIDS ; ENERGY ; BEHAVIOR ; CONFORMATIONAL SWITCH ; GP120 ; HIV-1 ; CHAIN ; RE ; interaction ; HIV ; SWITCH ; USA ; POLARITY ; GAUSSIAN-BASIS SETS ; MEDIA ; ATOMS LI ; interactions ; amino acids ; POSITION ; APPROXIMATE COULOMB POTENTIALS ; AUXILIARY BASIS-SETS ; KR ; PI INTERACTIONS
    Abstract: A 15-residue sequence (LPCRIKQFINMWQEV) forming the principal CD4-binding domain of gp120 from HIV 1 displays unusual, highly cooperative refolding from beta-hairpin to 3(10) helix when the polarity of the surrounding medium drops below a critical point, the so-called conformational switch. The tryptophan at position 12 has been shown to be essential for the cooperativity of the refolding process, and several lines of evidence from earlier work had suggested that it was the aromatic quadrupole that was responsible for this. To de. ne more precisely what physico-chemical properties of tryptophan brought about the unique behavior of this peptide, nonproteogenic aromatic amino acids have been selected based on desired alterations in quadrupole moment, electrostatic potential surface, and binding energy to ions. These were built into the peptide in the place of tryptophan and their effect on switch behavior examined. It could be shown that a minimal strength of the quadrupole moment is necessary but not sufficient to enforce cooperativity of refolding, with other properties of tryptophan playing a role in the optimum interaction of this residue with other side chains of the peptide
    Type of Publication: Journal article published
    PubMed ID: 18599633
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: ENVIRONMENT ; APOPTOSIS ; EXPRESSION ; GROWTH ; tumor ; CELL ; Germany ; human ; KINASE ; SITE ; TISSUE ; BINDING ; BIOLOGY ; fibroblasts ; MOLECULAR-BIOLOGY ; PHOSPHORYLATION ; ACID ; DESIGN ; MODULATION ; DERIVATIVES ; LIGANDS ; NETHERLANDS ; LECTIN ; STRUCTURAL-CHANGES ; HUMAN NEUROBLASTOMA-CELLS ; molecular biology ; molecular ; RE ; INCREASE ; NUCLEAR ; enzymatic ; modification ; FUNCTIONALITY ; amino acids ; MAMMALIAN LECTINS ; CARBOHYDRATE-BINDING PROTEIN-35 ; GANGLIOSIDE GM(1) ; histochemistry ; serine phosphorylation ; titania chromatography
    Abstract: Galectin-3 has a unique modular design. Its short N-terminal stretch can be phosphorylated, relevant for nuclear export and anti-anoikis/apoptosis activity. Enzymatic modification by casein kinase 1 at constant ATP concentration yielded mg quantities of mono- and diphosphorylated derivatives at Ser5/Ser11 in a 2:1 ratio. Their carbohydrate-inhibitable binding to asialofetuin, cell surfaces of three tumor lines, rabbit erythrocytes leading to haemagglutination and cytoplasmic sites in fixed tissue sections was not markedly altered relative to phosphate-free galectin-3. Spectroscopically, phosphorylation induced alterations in the far UV CD, indicative of an increase in ordered structure. This is accompanied by changes in the environment of aromatic amino acids signified by shifts in the near UV CD. (C) 2008 Elsevier B.V. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18302943
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: PEPTIDE ; IN-VITRO ; Germany ; MODEL ; GENERATION ; DISEASE ; antibodies ; antibody ; OLIGOMERS ; BETA ; PRECURSOR PROTEIN ; SECONDARY STRUCTURE ; DIMER ; FIBRILS ; SENILE PLAQUES
    Type of Publication: Journal article published
    PubMed ID: 12840025
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: PEPTIDE ; RECEPTOR ; Germany ; DISTINCT ; PROTEIN ; PROTEINS ; SEQUENCE ; SEQUENCES ; DESIGN ; MEMBRANE ; FUSION ; PEPTIDES ; SERIES ; AMINO-ACIDS ; SECONDARY STRUCTURE ; DE-NOVO ; RECEPTORS ; FLEXIBILITY ; MEMBRANES ; MEMBRANE PROTEIN ; MEMBRANE-PROTEIN ; SEGMENT ; RESIDUES ; ENVIRONMENTS ; GLYCINE ; INFLUENZA HEMAGGLUTININ ; INFRARED-SPECTROSCOPY ; PROPENSITIES ; SNARE PROTEINS ; SPANNING DOMAIN ; VIRUS G-PROTEIN
    Abstract: Fusion of biological membranes is mediated by distinct integral membrane proteins, e.g., soluble N-ethylmaleimide-sensitive factor attachment protein receptors and viral fusion proteins. Previous work has indicated that the transmembrane segments (TMSs) of such integral membrane proteins play an important role in fusion. Furthermore, peptide mimics of the transmembrane part can drive the fusion of liposomes, and evidence had been obtained that fusogenicity depends on their conformational flexibility. To test this hypothesis, we present a series of unnatural TMSs that were designed de novo based on the structural properties of hydrophobic residues. We find that the fusogenicity of these peptides depends on the ratio of alpha-helix-promoting Leu and beta-sheet-promoting Val residues and is enhanced by helix-destabilizing Pro and Gly residues within their hydrophobic cores. The ability of these peptides to refold from an alpha-helical state to a beta-sheet conformation and backwards was determined under different conditions. Membrane fusogenic peptides with mixed Leu/ Val sequences tend to switch more readily between different conformations than a nonfusogenic peptide with an oligo-Leu core. We propose that structural flexibility of these TMSs is a prerequisite of fusogenicity
    Type of Publication: Journal article published
    PubMed ID: 15456911
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: PEPTIDE ; Germany ; TOOL ; DOMAIN ; SEQUENCE ; CRYSTAL-STRUCTURE ; PEPTIDES ; STABILITY ; FRAGMENTS ; PREDICTION ; INITIATION ; CLUSTER ; PROGRAM ; RE ; COILED-COIL ; CONFORMATION ; BETA-SHEET PROTEINS ; BUNDLE PROTEIN ; DE-NOVO DESIGN ; HAIRPIN PEPTIDE ; protein structure ; structure stability ; TRANSITION-STATE
    Abstract: The side chain interaction index (SCII) is a method of calculating the propensity for short-range interactions among side chains within a peptide sequence. Here, it is shown that the SCII values of secondary structure elements that have been shown to fold early and independently cluster separately from those of structures that fold later and/or are dependent on long-range interactions. In addition, the SCII values of engineered peptides that spontaneously adopt a particular desired fold in solution are significantly different from those of engineered peptides that fail to exhibit a stable conformation. Thus, the SCII, as a measure of local structural stability, constitutes a useful tool in folding prediction and in protein/peptide engineering. A program that allows rapid calculation of SCIT values is presented. (c) 2006 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16860775
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...