scholarly journals Organometallic chemical biology: an organometallic approach to bioconjugation

2017 ◽  
Vol 89 (11) ◽  
pp. 1619-1640 ◽  
Author(s):  
Ekaterina V. Vinogradova

AbstractThis review summarizes the history and recent developments of the field of organometallic chemical biology with a particular emphasis on the development of novel bioconjugation approaches. Over the years, numerous transformations have emerged for biomolecule modification with the use of organometallic reagents; these include [3+2] cycloadditions, C–C, C–S, C–N, and C–O bond forming processes, as well as metal-mediated deprotection (“decaging”) reactions. These conceptually new additions to the chemical biology toolkit highlight the potential of organometallic chemistry to make a significant impact in the field of chemical biology by providing further opportunities for the development of chemoselective, site-specific and spatially resolved methods for biomolecule structure and function manipulation. Examples of these transformations, as well as existing challenges and future prospects of this rapidly developing field are highlighted in this review.

2020 ◽  
Vol 74 (9) ◽  
pp. 681-688 ◽  
Author(s):  
Eva Hevia

Core tools of synthetic chemistry, polar organometallic reagents (typified by organolithium and Grignard reagents) are used worldwide for constructing compounds, especially aromatic compounds, which are ubiquitous in organic chemistry and thus in numerous commodities essential to everyday life. By isolation and characterisation of key organometallic intermediates, research in our group has led to the design of polar mixed-metal reagents imbued with synergistic effects that display chemical properties and reactivity profiles far exceeding the limits of traditional single-metal reagents. These studies have improved existing, or established new fundamentally important, synthetic methodologies based on either stoichiometric or catalytic reactions. Bimetallic cooperative effects have been demonstrated in an impressive array of important bond forming reactions including deprotonative metallation, transition metal-free C–C bond formation and metal–halogen exchange to name just a few. Towards greener, more sustainable, safer chemical transformations, our group has also pioneered the use of polar organometallic reagents under air and/or with water present using biorenewable solvents such as Deep Eutectic Solvents (DES) and 2-methyl THF. Herein we summarize some of our recent efforts in this intriguing area, which we believe can make inroads towards a step change in the practice and future scope of polar organometallic chemistry.


2020 ◽  
Author(s):  
Inga Boll ◽  
Pia Jensen ◽  
Veit Schwämmle ◽  
Martin R. Larsen

AbstractSynaptic transmission leading to release of neurotransmitters in the nervous system is a fast and highly dynamic process. Previously, protein interaction and phosphorylation have been thought to be the main regulators of synaptic transmission. Here we show a novel potential modulator of synaptic transmission, sialylation of N-linked glycosylation. The negatively charged sialic acids can be modulated, similarly to phosphorylation, by the action of sialyltransferases and sialidases thereby changing local structure and function of membrane glycoproteins. We characterized site-specific alteration in sialylation on N-linked glycoproteins in isolated rat nerve terminals after brief depolarization using quantitative sialiomics. We identified 1965 formerly sialylated N-linked glycosites in synaptic proteins and found that the abundances of 430 glycosites changed after five seconds depolarization. We observed changes on essential synaptic proteins such as synaptic vesicle proteins, ion channels and transporters, neurotransmitter receptors and cell adhesion molecules. This study is to our knowledge the first to describe ultra-fast site-specific modulation of the sialiome after brief stimulation of a biological system.


2005 ◽  
Vol 62 (6) ◽  
pp. 1254-1270 ◽  
Author(s):  
John C Brazner ◽  
Danny K Tanner ◽  
Naomi E Detenbeck ◽  
Sharon L Batterman ◽  
Stacey L Stark ◽  
...  

The relative importance of regional, watershed, and in-stream environmental factors on fish assemblage structure and function was investigated in western Lake Superior tributaries. We selected 48 second- and third-order watersheds from two hydrogeomorphic regions to examine fish assemblage response to differences in forest fragmentation, watershed storage, and a number of other watershed, riparian, and in-stream habitat conditions. Although a variety of regional, fragmentation, and storage-related factors had significant influences on the fish assemblages, water temperature appeared to be the single most important environmental factor. We found lower water temperatures and trout–sculpin assemblages at lower fragmentation sites and higher temperatures and minnow–sucker–darter assemblages as storage increased. Factors related to riparian shading and flow separated brook trout streams from brown trout (Salmo trutta) – rainbow trout (Oncorhynchus mykiss) streams. Functionally, fish assemblages at lower fragmentation sites were dominated by cold-water fishes that had low silt tolerance and preferred moderate current speeds, while fishes with higher silt tolerances, warmer temperature preferences, and weaker sustained swimming capabilities were most common at higher storage sites. Our results suggest that site-specific environmental conditions are highly dependent on regional- and watershed-scale characters and that a combination of these factors operates in concert to influence the structure and function of stream fish assemblages.


1988 ◽  
Vol 15 (2) ◽  
pp. 27 ◽  
Author(s):  
C Critchley

In this paper, the evidence supporting two different models for the molecular mechanism of photoinhibition is discussed. One hypothesis centres around the suggestion that photoinhibition is due to the loss of the herbicide-binding Dl polypeptide of photosystem II. The other model suggests that damage to a functional group in the reaction centre is the primary cause of photoinhibition. In order to put the apparent controversy into context, recent developments in our understanding of the structure and function of the photosystem II reaction centre are described. Interpretation and judgement of all available evidence suggest primary photoinhibitory damage to be incurred by the reaction-centre chlorophyll P680 destabilising the apoprotein(s) and eventually resulting in their proteolytic degradation and removal from the photosystem II complex and the thylakoid membrane.


1998 ◽  
Vol 4 (6) ◽  
pp. 689-690
Author(s):  
Jarl Risberg

Imaging of the structure and function of the human brain has grown to an area with increasing impact on neuropsychological research as well as on the routine clinical evaluation of brain damaged patients. The scientific and popular literature is now flooded by increasingly more spectacular pictures of the brain. The images no longer only illustrate what is well known from earlier research but they do also sometimes provide information of importance for the further development of neuropsychological theories. The two volumes edited by Erin D. Bigler, Neuroimaging I and II, offer a possibility for neuropsychologists and other interested readers to get acquainted with the more recent developments in measurement technology and applications in basic science (Volume I) as well as in the clinic (Volume II). The authors of the 24 chapters are generally outstanding researchers, with impressive expertise within their fields of specialization.


2017 ◽  
Vol 46 (4) ◽  
pp. 1052-1079 ◽  
Author(s):  
Anouk S. Lubbe ◽  
Wiktor Szymanski ◽  
Ben L. Feringa

A critical overview is given of recent applications of molecular photoswitches to modulate DNA and RNA structure and function.


2017 ◽  
Vol 45 (2) ◽  
pp. 555-562 ◽  
Author(s):  
James S. Italia ◽  
Yunan Zheng ◽  
Rachel E. Kelemen ◽  
Sarah B. Erickson ◽  
Partha S. Addy ◽  
...  

In the last two decades, unnatural amino acid (UAA) mutagenesis has emerged as a powerful new method to probe and engineer protein structure and function. This technology enables precise incorporation of a rapidly expanding repertoire of UAAs into predefined sites of a target protein expressed in living cells. Owing to the small footprint of these genetically encoded UAAs and the large variety of enabling functionalities they offer, this technology has tremendous potential for deciphering the delicate and complex biology of the mammalian cells. Over the last few years, exciting progress has been made toward expanding the toolbox of genetically encoded UAAs in mammalian cells, improving the efficiency of their incorporation and developing innovative applications. Here, we provide our perspective on these recent developments and highlight the current challenges that must be overcome to realize the full potential of this technology.


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