1,736 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
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
Stereoselective Synthesis of Brevianamide E
No full textThe hydroxypyrroloindolenine (Hpi) motif forms the fundamental core of the pentacyclic natural product, brevianamide E, the concise stereoselective synthesis of which, via oxidative cyclization, is described.</p
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
Perrin Numbers That Are Concatenations of a Perrin Number and a Padovan Number in Base b
No full textLet (Formula presented.) be a Padovan sequence and (Formula presented.) be a Perrin sequence. Let n, m, b, and k be non-negative integers, where (Formula presented.). In this paper, we are devoted to delving into the equations (Formula presented.) and (Formula presented.), where d is the number of digits of (Formula presented.) or (Formula presented.) in base b. We show that the sets of solutions are (Formula presented.) (Formula presented.) for the first equation and (Formula presented.) for the second equation. Our approach employs advanced techniques in Diophantine analysis, including linear forms in logarithms, continued fractions, and the properties of Padovan and Perrin sequences in base b. We investigate both the deep structural symmetries and the complex structures that connect recurrence relations and logarithmic forms within Diophantine equations involving special number sequences. © 2025 by the author
L’action ou la contemplation. Note sur la relation de la fille de Thrace au Docteur angélique
No full textIf the opposition between “action and contemplation” seems characteristic of the history of philosophy, it also sums up Hannah Arendt’s personal history and philosophy – the diagnosis of the theoretician of the political practice on her contemporaries being eloquent. But the author of the Human condition invites us to reverse the conjunction. Arendt breaks up deliberately with philosophical tradition and particularly with Thomas Aquinas by making these terms exclusive and choosing to think either action (without contemplation) or contemplation (without action). We would like thus to reflect on the relationship between these two thinkers by examining potential echoes of Summa Theologiae within Arendt’s 1958 essay
Overdose : Heartbreak and hope in Canada's opioid crisis
No full textProfessor Perrin’s research covers issues related to victims of crime, and the opioid crisis. He is an advocate for compassionate, evidence-based approaches to pressing criminal justice and societal issues. Professor Perrin is the author of numerous law review articles and provides commentary in the media. His books include Overdose: Heartbreak and Hope in Canada’s Opioid Crisis (2020), Victim Law: The Law of Victims of Crime in Canada (2017) and Invisible Chains: Canada’s Underground World of Human Trafficking (2011). Professor Perrin joined UBC after serving as a law clerk at the Supreme Court of Canada and advising judges at the International Criminal Tribunal for the former Yugoslavia and Special Court for the Sierra Leone. He was lead criminal justice advisor and in-house legal counsel to the Prime Minister of Canada.Law, Peter A. Allard School ofUnreviewedFacult
sj-docx-1-ine-10.1177_15910199231157926 - Supplemental material for A novel histological occlusion classification for coiled aneurysms based on multiphoton microscopy
No full textSupplemental material, sj-docx-1-ine-10.1177_15910199231157926 for A novel histological occlusion classification for coiled aneurysms based on multiphoton microscopy by Szatmary Zoltan, Cortese Jonathan, Mounier Jeremy and
Perrin Marie-Laure, Janot Kevin, Couquet Claude,
Aurélien Le Flahec, Leger-Bretou Claire, Mounayer Charbel, Rouchaud Aymeric, Sylvia M Bardet in Interventional Neuroradiology</p
Synthesis, characterisation, and in vitro evaluation of pro <sup>2</sup>-Ile<sup>3</sup>-S-deoxo-amaninamide and pro<sup>2</sup>-D-allo- Ile<sup>3</sup>-5-deoxo-amaninamide: Implications for structure-activity relationships in amanitin conformation and toxicity
No full textThe amatoxins are a family of toxic bicyclic peptides that inhibit RNA polymerase II. Herein we discuss an improved synthesis of these compounds from easily obtainable amino acids by means of a solid-phase methodology. Interestingly, we obtained two products of the same mass following our final macrocyclisation, relating to a similar distribution of products described in some previous reports. One of these products was the desired amatoxin ; Pro 2-Ile3-S-deoxo-amaninamide 1b. The other compound, after thorough investigation, was confirmed to be the epimer Pro2-D-allo- Ile3-S-deoxoamaninamide 1a, not an atropisomer structure as previously suggested in syntheses of related amanitin analogues. Crystallographic data of 1a confirms the presence of a βII-turn, rather than a βI-turn common to the natural toxin and 1b. This difference explains the large variation in CD spectra, although it seems to have relatively little effect on the bioactivity in vitro. These data provide new insights into the bicyclic amatoxin structure.</p
Covalent Schiff Base Catalysis and Turnover by a DNAzyme: A M <sup>2+</sup>-Independent AP-Endonuclease Mimic
No full textA DNAzyme, synthetically modified with both primary amines and imidazoles, is found to act as a M2+-independent AP lyase-endonuclease. In the course of the cleavage reaction, this DNAzyme forms a covalent Schiff base intermediate with an abasic site on a complementary oligodeoxyribonucleotide. This intermediate, which is inferred from NaCNBH3 trapping as well as cyanide inhibition, does not evidently accumulate because the second step, dehydrophosphorylative elimination, is fast compared to Schiff base formation. The 5′-product that remains linked to the catalyst hydrolyzes slowly to regenerate free catalyst. The use of duly modified DNAzymes to perform Schiff base catalysis demonstrates the value of modified nucleotides for enhancing the catalytic repertoire of nucleic acids. This work suggests that DNAzymes will be capable of catalyzing aldol condensation reactions.</p
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