1,721,066 research outputs found
Tryptathionine bridges in peptide synthesis
No full textThe tryptathionine linkage is a crosslink formed between tryptophan and cysteine. This feature is characteristic of the bicyclic peptides: the phallotoxins and the amatoxins. These peptides both bind to protein folds of their respective targets (F-actin and RNA pol II, respectively) with extremely high affinities. Studies on these peptides have shown that the tryptathionine crosslink is essential for this binding affinity. Tryptathionines have been investigated for many years and several syntheses exist for their formation. In this review, we report on the various methodologies employed in tryptathionine synthesis, and discuss some of the advantages and disadvantages associated with each of them.</p
Thermosensitive liposomes in cancer therapy
No full textThermosensitive liposomes have been a popular area of investigation for several years leading to a plentitude of scientific literature and several patents. The majority of formulations are still in the early stage of development and preclinical testing, although one formulation, ThermoDox®, is significantly more advanced. This formulation is now in clinical trials for a few different cancer indications. In this review, key patents and publications through the evolution of thermosensitive lipososomes are presented, including the use of polymers, lipids and other molecules to control the temperature sensitivity. ThermoDox® is discussed with an update on recent experiments and reports from the clinical trials. Finally, a summary of recent formulations designed to improve upon the ThermoDox® benchmark is presented, and the challenges and future directions for thermosensitive liposome technology are discussed.</p
Intraannular savige-fontana reaction: One-step conversion of one class of monocyclic peptides into another class of bicyclic peptides
No full textCyclisation and cross-linking strategies are important for the synthesis of cyclic and bicyclic peptides. These macrolactams are of great interest due to their increased biological activity compared to linear analogues. Herein, we describe the synthesis of a cyclic peptide containing an Hpi toxicophore, reminiscent of phakellistatins and omphalotins. The first intraannular cross-linking of such a peptide is then presented: using neat TFA to catalyse a Savige-Fontana tryptathionylation, the Hpi-containing peptide is converted to a bicyclic amatoxin analogue. As such, this methodology represents an efficient cyclisation method for cross-linking peptides and exposes a heretofore unrealised relationship between two different classes of peptide natural products. This finding increases the degree of potential chemical space for library generation.</p
Development of oligonucleotide probes for genetic analysis
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Diastereoselectivity in the synthesis of syn-cis-3a-hydroxypyrrolo[2,3-b] indoline N<sup>α′</sup>-methyl-dipeptide methyl esters
No full textDescribed herein is a high yielding, diastereoselective synthesis of the syn-cis hydroxypyrroloindoline moiety by oxidation of the Nα-trityl- tryptophan-Nα-methyl-dipeptide methyl esters.</p
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Hyperthermia-induced drug targeting
No full textIntroduction: Specific delivery of a drug to a target site is a major goal of drug delivery research. Using temperature-sensitive liposomes (TSLs) is one way to achieve this; the liposome acts as a protective carrier, allowing increased drug to flow through the bloodstream by minimizing clearance and non-specific uptake. On reaching microvessels within a heated tumor, the drug is released and quickly penetrates. A major advance in the field is ThermoDox® (Celsion), demonstrating significant improvements to the drug release rates and drug uptake in heated tumors (∼ 41°C). Most recently, magnetic resonance-guided focused ultrasound (MRgFUS) has been combined with TSL drug delivery to provide localized chemotherapy with simultaneous quantification of drug release within the tumor. Areas covered: In this article the field of hyperthermia-induced drug delivery is discussed, with an emphasis on the development of TSLs and their combination with hyperthermia (both mild and ablative) in cancer therapy. State-of-the-art image-guided heating technologies used with this combination strategy will also be presented, with examples of real-time monitoring of drug delivery and prediction of efficacy. Expert opinion: The specific delivery of drugs by combining hyperthermia with TSLs is showing great promise in the clinic and its potential will be even greater as the use of image-guided focused ultrasound becomes more widespread-a technique capable of penetrating deep within the body to heat a specific area with improved control. In conjunction with this, it is anticipated that multifunctional TSLs will be a major topic of study in this field.</p
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