scholarly journals Synthesis of O6-alkylated preQ1 derivatives

2021 ◽  
Vol 17 ◽  
pp. 2295-2301
Author(s):  
Laurin Flemmich ◽  
Sarah Moreno ◽  
Ronald Micura
Keyword(s):  
Cytosine Methylation ◽  
Hydration Reaction ◽  
Reaction Sequence ◽  
Group Transfer ◽  
Naturally Occurring ◽  
Rna Labeling ◽  
Oxime Formation ◽  
Solid Foundation ◽  
Methyl Group Transfer

A naturally occurring riboswitch can utilize 7-aminomethyl-O6-methyl-7-deazaguanine (m6preQ1) as cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues for the development of RNA labeling tools based on tailored O6-alkylated preQ1 derivatives. Here, we report a robust synthesis for this class of pyrrolo[2,3-d]pyrimidines starting from readily accessible N2-pivaloyl-protected 6-chloro-7-cyano-7-deazaguanine. Substitution of the 6-chloro atom with the alcoholate of interest proceeds straightforward. The transformation of the 7-cyano substituent into the required aminomethyl group turned out to be challenging and was solved by a hydration reaction sequence on a well-soluble dimethoxytritylated precursor via in situ oxime formation. The synthetic path now provides a solid foundation to access O6-alkylated 7-aminomethyl-7-deazaguanines for the development of RNA labeling tools based on the preQ1 class-I riboswitch scaffold.

How Artefacts Do Leadership: A Ventriloquial Analysis

2021 ◽  
pp. 089331892199807
Author(s):  
Jonathan Clifton ◽  
Fernando Fachin ◽  
François Cooren
Keyword(s):  
Organizational Communication ◽  
Recent Work ◽  
Distributed Leadership ◽  
Network Theory ◽  
Actor Network Theory ◽  
Fine Grained ◽  
Naturally Occurring ◽  
Human Actors

To date there has been little work that uses fine-grained interactional analyses of the in situ doing of leadership to make visible the role of non-human as well as human actants in this process. Using transcripts of naturally-occurring interaction as data, this study seeks to show how leadership is co-achieved by artefacts as an in-situ accomplishment. To do this we situate this study within recent work on distributed leadership and argue that it is not only distributed across human actors, but also across networks that include both human and non-human actors. Taking a discursive approach to leadership, we draw on Actor Network Theory and adopt a ventriloquial approach to sociomateriality as inspired by the Montreal School of organizational communication. Findings indicate that artefacts “do” leadership when a hybrid presence is made relevant to the interaction and when this presence provides authoritative grounds for influencing others to achieve the group’s goals.

scholarly journals Novel insights into the m6A-RNA methyltransferase METTL3 in cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yiqing Cai ◽  
Rui Feng ◽  
Tiange Lu ◽  
Xiaomin Chen ◽  
Xiangxiang Zhou ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Human Cancer ◽  
Rna Modification ◽  
Rapid Progression ◽  
Antitumor Therapy ◽  
Promoting Effect ◽  
Methyl Group ◽  
Group Transfer ◽  
Functional Regulation ◽  
Methyl Group Transfer

AbstractN6-methyladenosine (m6A) is a prevalent internal RNA modification in higher eukaryotic cells. As the pivotal m6A regulator, RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of m6A modification. This epigenetic regulation contributes to the structure and functional regulation of RNA and further promotes tumorigenesis and tumor progression. Accumulating evidence has illustrated the pivotal roles of METTL3 in a variety of human cancers. Here, we systemically summarize the interaction between METTL3 and RNAs, and illustrate the multiple functions of METTL3 in human cancer. METLL3 is aberrantly expressed in a variety of tumors. Elevation of METTL3 is usually associated with rapid progression and poor prognosis of tumors. On the other hand, METTL3 may also function as a tumor suppressor in several cancers. Based on the tumor-promoting effect of METTL3, the possibility of applying METTL3 inhibitors is further discussed, which is expected to provide novel insights into antitumor therapy.

Absorption of beta-casomorphins from autoperfused lamb and piglet small intestine

1990 ◽  
Vol 259 (3) ◽  
pp. G443-G452 ◽  
Author(s):  
L. C. Read ◽  
A. P. Lord ◽  
V. Brantl ◽  
G. Koch
Keyword(s):  
Small Intestine ◽  
Intestinal Lumen ◽  
Physiological Conditions ◽  
Naturally Occurring ◽  
Gut Epithelium ◽  
Measured Absorption ◽  
Beta Casein ◽  
Kinetics Of

beta-Casomorphins (beta-CMs) derived from milk beta-casein may exert various opiate activities in milk-fed infants. To assess the physiological significance of beta-CMs as a source of circulating opioids in infants, we measured absorption rates of several beta-CMs under near-physiological conditions using in situ autoperfused lamb intestine. The naturally occurring beta-CMs, beta-CM-7 and beta-CM-4-amide, were absorbed readily into blood with no transfer into lymph. Uptake peaked within several minutes of the luminal infusion of peptide but then declined sharply and stopped within a further 10-15 min. The recovery in blood, intestinal contents, and tissue at the end of the 30-min experiment was less than 1% of the infused dose. The low recovery was due to rapid proteolysis based on in vitro studies that demonstrated half-lives of less than 5 min in lamb blood, luminal contents, and lymph. The synthetic dipeptidyl peptidase IV-resistant analogue beta-[D-Ala2]CM- 4-amide was stable during incubation in blood, lymph, or luminal contents and was absorbed into blood at rates that were maximal within several minutes and remained steady for the 30-min period. We conclude that although natural beta-CMs are transferred across the lamb small intestine, rapid degradation within the intestinal lumen, gut epithelium, and blood would prevent entry into the circulation under normal conditions. Val-beta-CM-7, a putative stable precursor, had similar stability and kinetics of absorption to beta-CM-7, results that exclude Val-beta-CM-7 as a stable precursor for delivery of beta-CMs to the circulation. Essentially identical results to those in lambs were obtained in 7-day-old piglets.

scholarly journals Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

2013 ◽  
Vol 9 ◽  
pp. 974-982 ◽  
Author(s):  
Tamashree Ghosh ◽  
Abhishek Santra ◽  
Anup Kumar Misra
Keyword(s):  
Reaction Sequence ◽  
Reaction Conditions ◽  
One Pot ◽  
Carbon Tetrabromide

A series of glycosyl hemiacetal derivatives have been transformed into thioglycosides and glycosyl thiols in a one-pot two-step reaction sequence mediated by Appel reagent (carbon tetrabromide and triphenylphosphine). 1,2-trans-Thioglycosides and β-glycosyl thiol derivatives were stereoselectively formed by the reaction of the in situ generated glycosyl bromides with thiols and sodium carbonotrithioate. The reaction conditions are reasonably simple and yields were very good.

Methyl group transfer upon gas phase decomposition of protonated methyl benzoate and similar compounds

2018 ◽  
Vol 53 (5) ◽  
pp. 379-384 ◽  
Author(s):  
Rafał Frański ◽  
Błażej Gierczyk ◽  
Maciej Zalas ◽  
Wojciech Jankowski ◽  
Marcin Hoffmann
Keyword(s):  
Gas Phase ◽  
Methyl Benzoate ◽  
Phase Decomposition ◽  
Methyl Group ◽  
Group Transfer ◽  
Methyl Group Transfer
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