Chemical biology of in vivo and in vitro wounds

1968 ◽  
Vol 17 ◽  
pp. 19-26 ◽  
Author(s):  
J.C. Houck ◽  
J. Johnston ◽  
R.A. Jacob
Keyword(s):  
Chemical Biology

scholarly journals Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl

2015 ◽  
Vol 112 (34) ◽  
pp. E4651-E4660 ◽  
Author(s):  
Miriam M. Cortese-Krott ◽  
Gunter G. C. Kuhnle ◽  
Alex Dyson ◽  
Bernadette O. Fernandez ◽  
Marian Grman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chemical Reactions ◽  
Chemical Biology ◽  
Arterial Compliance ◽  
Cardiac Contractility ◽  
Reaction Products ◽  
Hybrid Species ◽  
Redox Switching

Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H2S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO−), polysulfides, and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO− is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO− synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N2O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H2S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.

scholarly journals Human ribosomal G-quadruplexes regulate heme bioavailability

2020 ◽  
Vol 295 (44) ◽  
pp. 14855-14865 ◽  
Author(s):  
Santi Mestre-Fos ◽  
Chieri Ito ◽  
Courtney M. Moore ◽  
Amit R. Reddi ◽  
Loren Dean Williams
Keyword(s):  
Chemical Biology ◽  
Human Cells ◽  
Affinity Reagents ◽  
In Cells

The in vitro formation of stable G-quadruplexes (G4s) in human rRNA was recently reported. However, their formation in cells and their cellular roles were not resolved. Here, by taking a chemical biology approach that integrates results from immunofluorescence, G4 ligands, heme-affinity reagents, and a genetically encoded fluorescent heme sensor, we report that human ribosomes can form G4s in vivo that regulate heme bioavailability. Immunofluorescence experiments indicate that the vast majority of extra-nuclear G4s are associated with rRNA. Moreover, titrating human cells with a G4 ligand alters the ability of ribosomes to bind heme and disrupts cellular heme bioavailability as measured by a genetically encoded fluorescent heme sensor. Overall, these results suggest that ribosomes play a role in regulating heme homeostasis.

scholarly journals Molecular Design in Practice: A Review of Selected Projects in a French Research Institute That Illustrates the Link between Chemical Biology and Medicinal Chemistry

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6083
Author(s):  
Benoit Deprez ◽  
Damien Bosc ◽  
Julie Charton ◽  
Cyril Couturier ◽  
Rebecca Deprez-Poulain ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Chemical Biology ◽  
Molecular Design ◽  
Chemical Space ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Human Beings ◽  
Molecular Components

Chemical biology and drug discovery are two scientific activities that pursue different goals but complement each other. The former is an interventional science that aims at understanding living systems through the modulation of its molecular components with compounds designed for this purpose. The latter is the art of designing drug candidates, i.e., molecules that act on selected molecular components of human beings and display, as a candidate treatment, the best reachable risk benefit ratio. In chemical biology, the compound is the means to understand biology, whereas in drug discovery, the compound is the goal. The toolbox they share includes biological and chemical analytic technologies, cell and whole-body imaging, and exploring the chemical space through state-of-the-art design and synthesis tools. In this article, we examine several tools shared by drug discovery and chemical biology through selected examples taken from research projects conducted in our institute in the last decade. These examples illustrate the design of chemical probes and tools to identify and validate new targets, to quantify target engagement in vitro and in vivo, to discover hits and to optimize pharmacokinetic properties with the control of compound concentration both spatially and temporally in the various biophases of a biological system.

scholarly journals Biotechnological Applications of Protein Splicing

2019 ◽  
Vol 20 (5) ◽  
pp. 408-424 ◽  
Author(s):  
Corina Sarmiento ◽  
Julio A. Camarero
Keyword(s):  
Protein Engineering ◽  
Chemical Biology ◽  
Protein Splicing ◽  
Biotechnological Applications ◽  
General Introduction ◽  
Recombinant Polypeptide ◽  
Affinity Tags ◽  
Novel Approaches

Protein splicing domains, also called inteins, have become a powerful biotechnological tool for applications involving molecular biology and protein engineering. Early applications of inteins focused on self-cleaving affinity tags, generation of recombinant polypeptide α-thioesters for the production of semisynthetic proteins and backbone cyclized polypeptides. The discovery of naturallyoccurring split-inteins has allowed the development of novel approaches for the selective modification of proteins both in vitro and in vivo. This review gives a general introduction to protein splicing with a focus on their role in expanding the applications of intein-based technologies in protein engineering and chemical biology.

scholarly journals Human Ribosomal G-Quadruplexes Regulate Heme Bioavailability

2020 ◽  
Author(s):  
Santi Mestre-Fos ◽  
Chieri Ito ◽  
Courtney M. Moore ◽  
Amit R. Reddi ◽  
Loren Dean Williams
Keyword(s):  
Ribosomal Rna ◽  
Chemical Biology ◽  
Human Cells ◽  
Affinity Reagents ◽  
Heme Metabolism ◽  
In Cells

ABSTRACTThe in vitro formation of stable G-quadruplexes (G4s) in human ribosomal RNA (rRNA) was recently reported. However, their formation in cells and their cellular roles have not been resolved. Here, by taking a chemical biology approach that integrates results from immunofluorescence, G4 ligands, heme affinity reagents, and a genetically encoded fluorescent heme sensor, we report that human ribosomes can form G4s in vivo that regulate heme bioavailability. Immunofluorescence experiments indicate that the vast majority of extra-nuclear G4s are associated with rRNA. Moreover, titrating human cells with a G4 ligand alters the ability of ribosomes to bind heme and disrupts cellular heme bioavailability as measured by a genetically encoded fluorescent heme sensor. Overall, these results suggest ribosomes are central hubs of heme metabolism.

scholarly journals Chemical Biology Applied to the Study of Bacterial Pathogens

2014 ◽  
Vol 83 (2) ◽  
pp. 456-469 ◽  
Author(s):  
Rebecca Anthouard ◽  
Victor J. DiRita
Keyword(s):  
Gene Expression ◽  
Small Molecules ◽  
Chemical Biology ◽  
Bacterial Pathogens ◽  
Biological Mechanisms ◽  
Chemical Genomics ◽  
Potential Therapeutics ◽  
Proof Of Principle

In recent years, chemical biology and chemical genomics have been increasingly applied to the field of microbiology to uncover new potential therapeutics as well as to probe virulence mechanisms in pathogens. The approach offers some clear advantages, as identified compounds (i) can serve as a proof of principle for the applicability of drugs to specific targets; (ii) can serve as conditional effectors to explore the function of their targetsin vitroandin vivo; (iii) can be used to modulate gene expression in otherwise genetically intractable organisms; and (iv) can be tailored to a narrow or broad range of bacteria. This review highlights recent examples from the literature to illustrate how the use of small molecules has advanced discovery of novel potential treatments and has been applied to explore biological mechanisms underlying pathogenicity. We also use these examples to discuss practical considerations that are key to establishing a screening or discovery program. Finally, we discuss the advantages and challenges of different approaches and the methods that are emerging to address these challenges.

scholarly journals Synthetic promoter based azide biosensor toolkit to advance chemical-biology

2020 ◽  
Author(s):  
Chandra Kanth Bandi ◽  
Kyle S. Skalenko ◽  
Ayushi Agrawal ◽  
Neelan Sivaneri ◽  
Margaux Thiry ◽  
...  
Keyword(s):  
Chemical Biology ◽  
Fluorescent Protein ◽  
Low Cost ◽  
Expression System ◽  
Detection Methods ◽  
Synthetic Promoter ◽  
Bioorthogonal Reaction ◽  
Green Fluorescent

AbstractReal-time azide or azido-functionalized molecular detection inside living cells using bioorthogonal chemistry-based approaches has been revolutionary to advancing chemical-biology. These methods have enabled diverse applications ranging from understanding the role of cellular glycosylation pathways, identifying diseased cells, and targeting delivery of azido-based therapeutic drugs. However, while classical techniques were applicable only to in-vitro detection of such functional groups, even recent bioorthogonal based-detection methods require expensive sensing reagents and also cannot selectively identify inorganic azide. Here, we report an in-vivo synthetic promoter based azide biosensor toolkit to selectively detect azide anions. A promiscuous cyanate-specific promoter was engineered to detect azide and rapidly induce expression of green fluorescent protein (GFP) in Escherichia coli. Our synthetic azide operon allows highly-tunable GFP expression, outperforming the classic lac-operon, and also offers an alternative low-cost protein expression system. Finally, we showcase the utility of this toolkit for in-vivo bioorthogonal reaction biosensing and glycoengineering based applications.

Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

1982 ◽  
Vol 40 ◽  
pp. 142-145
Author(s):  
E. J. Kollar
Keyword(s):  
Connective Tissue ◽  
Oral Mucosa ◽  
Basal Lamina ◽  
Functional Derivatives ◽  
Specific Source ◽  
Dental Epithelium ◽  
Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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