196,096 research outputs found
Cyclic RGD Peptides Containing beta-Homoamino Acids: Synthesis and Biological Activity
No full textMüller A, Koksch M, Sewald N. Cyclic RGD Peptides Containing beta-Homoamino Acids: Synthesis and Biological Activity. In: J. Pept. Sci. 1998: 77-77
Are beta-Amino Acids gamma-Turn Mimetics ?
No full textMüller A, Schumann F, Koksch M, Sewald N. Are beta-Amino Acids gamma-Turn Mimetics ? In: J. Pept. Sci., Supplement. 2000: 69-69
Synthesis of Cyclic RGD-Peptides Containing beta-Amino Acids
No full textMüller A, Schumann F, Koksch M, Sewald N. Synthesis of Cyclic RGD-Peptides Containing beta-Amino Acids. Letters in Peptide Science. 1997;4(4):275-281
Are beta-amino acids gamma-turn mimetics? Exploring a new design principle for bioactive cyclopeptides
No full textSchumann F, Müller A, Koksch M, Müller G, Sewald N. Are beta-amino acids gamma-turn mimetics? Exploring a new design principle for bioactive cyclopeptides. Journal of the American Chemical Society. 2000;122(48):12009-12010
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses
No full textFollowing an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied
Evaluierung des Einflusses von Fluor auf die Amyloidbildung – eine systematische Studie an einem Coiled coil-basierten Modellpeptid
No full text1 Introduction 1 2 Properties of fluorinated amino acids 3 2.1 Fluorination of
aliphatic amino acids 3 2.2 Fluorination of aromatic amino acids 6 2.3
Fluorination of polar or charged amino acids 7 2.4 Fluorination of proline 8 3
Amyloids: regarding pathogenicity and potential biomaterials 11 3.1 The
phenomenon of aggregation and common structural characteristics of amyloids 11
3.2 Amyloidogenic structures found in diseases 14 3.3 Amyloid structures as
scaffolds and templates for biomaterials 17 4 Aliphatic fluorinated amino
acids in peptides and proteins 21 4.1 Fluorinated amino acids in helical
peptides 21 4.1.1 Proteolytic stability of fluorinated peptides 22 4.1.2
Hydrophobicity, packing, or the “fluorous effect” 23 4.1.3 Altered activity
and function of fluorinated peptides 27 4.2 Fluorinated amino acids in β-sheet
forming peptides 28 4.3 Fluorinated amino acids in amyloid forming peptides 32
4.3.1 Fluorinated amino acids as 19F-NMR-labels in amyloid structures 33 4.3.2
Fluorinated amino acids as tools to modulate amyloid fibrils 36 5 Aim of the
work 39 6 Applied Methods 41 6.1 Circular dichroism spectroscopy 41 6.2 Dye
Binding studies 44 6.3 Size exclusion / static light scattering 45 6.4 Solid
state 19F-NMR 48 6.4.1 The CODEX experiment 50 7 Results and discussion 53 7.1
The coiled coil as a model to study amyloid formation 53 7.2 The internal
fibril architecture of VW18 57 7.3 The impact of proline ring puckering on
turn conformations 62 7.3.1 The different turn motifs of β-hairpins and
amyloids 62 7.3.2 The effect of a glutamate side chain on proline’s ring
conformation 64 7.4 The role of oligomeric intermediates in the amyloid
formation process of VW18 72 7.5 Altering the amyloid formation process by
fluorinated amino acids 79 7.5.1 The fluorinated building blocks 80 7.5.2
Hydrophobicity and spatial demand of fluorinated amino acids 81 7.5.3 The
α-helix propensity of fluorinated amino acids 82 7.5.4 Amyloid formation rates
of fluorinated VW18 variants 86 7.5.5 Analysis of the overall VW18 fibril
structure by solid state 19F-NMR 91 7.5.6 The importance of the initial
structure on amyloid formation rates 95 8 Summary 101 9 Outlook 105 10
Experimental Section 109 10.1 General Methods 109 10.2 Synthesis of
fluorinated amino acids 109 10.2.1 Synthesis of
(S)-2-amino-4,4,4-trifluorobutanoic acid (TfeGly) (3)433,237 110 10.2.2
Synthesis of (S)-2-amino-4-fluorobutanoic acid (MfeGly) (1) 113 10.2.3
Synthesis of Fmoc protected TfV and TfI 114 10.3 Peptide synthesis,
purification and characterization 117 10.3.1 Automated peptide synthesis 117
10.3.2 Manual peptide synthesis 118 10.3.3 Capping 119 10.3.4 Cleavage from
the resin 119 10.3.5 Preparative HPLC 119 10.3.6 Analytical HPLC 120 10.3.7
Characterization by ESI-ToF 121 10.4 Synthesized peptides 121 10.5 Folding
studies 122 10.5.1 Sample preparation and concentration determination 122
10.5.2 pH adjustment 124 10.5.3 CD spectroscopy 124 10.5.4 α-helix propensity
measurements 125 10.5.5 HPLC assay to estimate the hydrophobicity and side
chain volume of the Fmoc-amino acids 125 10.5.6 Size exclusion / static light
scattering 126 10.5.7 Thioflavin T fluorescence staining assay 127 10.5.8
Transmission electron microscopy 127 10.5.9 Solution 1H-NMR spectroscopy of
P1_P variants 128 10.5.10 Solid-state 19F-NMR of VW18 variants containing
MfeGly 128 11 Literature 131Ein gemeinsames Merkmal vieler neurodegenerativer Erkrankungen ist die
strukturelle Umfaltung von Peptiden aus einer nativen, funktionalen
Konformation in unlösliche Amyloid-Ablagerungen. Amyloidbildung tritt aber
nicht nur im Zusammenhang mit Krankheiten auf, sondern ist eine generelle
Eigenschaft von Peptiden. Durch ihre besondere Stabilität und ihre
regelmäßigen Strukturen sind Amyloide mittlerweile auch interessante
Materialien für Bio- oder Nanotechnologische Anwendungen geworden. In dieser
Hinsicht wurde der Einbau nicht natürlicher Baussteine, insbesondere
fluorierter Aminosäuren, eine Standardstrategie um solche Strukturen zu
modifizieren. Durch seine besonderen stereoelektronischen Eigenschaften kann
Fluor die Struktur, die Funktion und die Stabilität von Peptiden und Proteinen
drastisch beeinflussen. Frühere Ansätze, die Eigenschaften fluorierter
Aminosäuren zu untersuchen, haben sich hauptsächlich auf helikale Systeme
beschränkt. In Amyloiden wurde Fluor bisher hauptsächlich als diagnostisches
Label eingebaut. Inwieweit Fluorierungen den Prozess der Amyloidbildung
beeinflussen wurde bisher nicht systematisch untersucht. Die vorliegende
Arbeit untersucht den Einfluss von Fluor auf die Amyloidbildung anhand eines
Modellpeptids, das in der Arbeitsgruppe von Frau Prof. Dr. B. Koksch
entwickelt wurde. Das Modell wurde so generiert, dass es unter kontrollierten
Bedingungen aus einer anfänglich helikalen Struktur in β-faltblattreiche
Amyloidstrukturen umfalten kann. Frühere Arbeiten lieferten fundierte
Erkenntnisse hinsichtlich der anfänglichen coiled coil-Struktur und des
internen Faltungsmotivs der Fibrille. Diese stellten die Grundlage für die
aktuellen Untersuchungen dar. Im Rahmen dieser Arbeit wurden zwei benachbarte
Valine, die eine Schlüsselfunktion für den Umfaltungsprozess darstellen durch
verschiedene fluorierte Aminosäuren ersetzt. Diese Aminosäuren unterschieden
sich hinsichtlich ihres Fluogehaltes und ihrer intrinsischen Eigenschaften,
wie Größe, Hydrophobie und α-Helixpropensität. Mithilfe des systematischen
Ansatzes wurden diese Eigenschaften fluorierter Aminosäuren hinsichtlich Ihres
Einflusses auf den Prozess der Amyloidbildung untersucht. Die Peptide, welche
mit einer Reihe von Methoden untersucht wurden, zeigten ein unerwartetes
Faltungsverhalten als Folge der variierten stereoelektronischen Eigenschaften,
die wiederum direkt auf den Einbau der jeweiligen Aminosäure zurückgeführt
werden konnten. Anhand von Berechnung der kritischen Größe des Nukleus, einem
Intermediat das als Templat für die Aggregation fungiert, konnte ein möglicher
Mechanismus für den Faltungsprozess vorgeschlagen werden. Die Ergebnisse
dieser Arbeit werden dazu beitragen den Prozess der Amyloidbildung und dessen
Modulation durch fluorierte Aminosäuren besser zu verstehen.A common hallmark of many neurodegenerative diseases is the conformational
transition of peptides from a native, functional form into insoluble amyloid
deposits. Amyloid formation, however, is not a specific feature of disease-
related proteins, but instead appears to be a general property of peptides and
proteins. The outstanding mechanical stability and remarkably regular fibrous
architecture have made amyloids also attractive materials for bio- or nano-
technological applications. In this regard nonnatural building blocks and
fluorinated amino acids in particular, have become standard tools for
modulating such structures. Due to its unique stereoelectronic properties
fluorine can have dramatic effects on structure, function, and stability of
peptides and proteins. Previous approaches to assessing the properties of
fluorinated amino acids have mainly focused on helical systems. In terms of
amyloid forming peptides, fluorine has mainly been used as diagnostic reporter
group. As to what extend fluorination influences the process of amyloid
formation has not been investigated systematically so far. The present thesis
evaluates the impact of fluorine on amyloid formation with the help of a model
peptide that was developed in the group of Prof. Dr. Beate Koksch. The model
was designed to provide an α-helical starting structure that can fold into
β-sheet rich amyloids under controlled conditions. Previous studies revealed
solid structural information about the initial coiled coil structure and the
final fibril architecture, which serve as a basis for the present
investigations. In the course of this work two neighboring valine residues
that play a key role in the structural transition were replaced by several
fluorinated amino acids that contain different fluorine content in their side
chains. These amino acids vary with regard to their intrinsic properties, such
as size, hydrophobicity, and secondary structure propensities. By means of
this systematic approach the properties of fluorinated amino acids have been
investigated for their impact on the amyloid formation process. The resulting
peptides, which have been analyzed by a battery of high and low resolution
techniques, show unexpected folding behaviors as a consequence of the
interplay between stereoelectronic effects that can be directly attributed to
the particular incorporated amino acid. By determining the critical size of
the nucleus, an intermediate species that serves as template for peptide
aggregation, a potential pathway for the structural transition has been
suggested. The results of this thesis will contribute to an understanding of
amyloid formation and how this process can be modulated by fluorinated amino
acids
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