Faculty Opinions recommendation of Structural diversity of supercoiled DNA.

2017 ◽  
Author(s):  
Wilma Olson
Keyword(s):  
Structural Diversity ◽  
Supercoiled Dna

scholarly journals Erratum: Structural diversity of supercoiled DNA

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Rossitza N. Irobalieva ◽  
Jonathan M. Fogg ◽  
Daniel J. Catanese ◽  
Thana Sutthibutpong ◽  
Muyuan Chen ◽  
...  
Keyword(s):  
Structural Diversity ◽  
Supercoiled Dna

scholarly journals Structural diversity of supercoiled DNA

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Rossitza N. Irobalieva ◽  
Jonathan M. Fogg ◽  
Daniel J. Catanese ◽  
Thana Sutthibutpong ◽  
Muyuan Chen ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Structural Diversity ◽  
Integrated Approach ◽  
Dna Supercoiling ◽  
Wide Distribution ◽  
Supercoiled Dna ◽  
Negative Supercoiling ◽  
Biochemical Analyses ◽  
Dynamics Simulations ◽  
Insight Into

Abstract By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

Metal-, and Organocatalyst-Free One-Pot Assembly of Chiral Aza-Tricyclic Molecules: Creating Six Contiguous Stereocenters from 2-D-Structures and an Amino Acid

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Amino Acid ◽  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Catalyst ◽  
Chiral Complex ◽  
Free Process

<p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> Practically, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for desired reactions. As a result, developing a method that enables rapid assembly of chiral complex molecules under metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward route to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“subcatalyst”) dual role of the intermediate enhances </a><a>the coordinational proximity of the chiral substrate and catalyst</a> in the key Aza-Michael/Michael cascade resulting in a substantial steric discrimination and an excellent overall diastereoselectivity. Whereas the “subcatalyst” (hidden catalyst) is not present in the reaction’s initial components, which renders a chiral catalyst-free process, it is strategically produced to promote sequential self-catalyzed reactions. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules and aid for the quest to create next generation of therapeutic agents.</p>

Antidiabetics: Structural Diversity of Molecules with a Common Aim

2018 ◽  
Vol 25 (18) ◽  
pp. 2140-2165 ◽  
Author(s):  
Jelena B. Popovic-Djordjevic ◽  
Ivana I. Jevtic ◽  
Tatjana P. Stanojkovic
Keyword(s):  
Structural Diversity ◽  
World Health ◽  
Common Disease ◽  
Peroxisome Proliferator ◽  
Epidemic Disease ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Health Organization

Background: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability. Methods: A systematic search of peer-reviewed scientific literature and public databases has been conducted. We included the most recent relevant research papers and data in respect to the focus of the present review. The quality of retrieved papers was assessed using standard tools. Results: The review highlights the chemical structural diversity of the molecules that have the common target-DMT2. So-called traditional antidiabetics as well as the newest and the least explored drugs include polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1, dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives, benzylthiazolidine- 2,4-diones (peroxisome proliferator activated receptor-γ agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules (α-glucosidase and sodium/ glucose co-transporter 2 inhibitors). Conclusion: As diabetes becomes a more common disease, interest in new pharmacological targets is on the rise.

Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions

2018 ◽  
Vol 25 (31) ◽  
pp. 3748-3767 ◽  
Author(s):  
Mohammed Benabdallah ◽  
Oualid Talhi ◽  
Fatiha Nouali ◽  
Nouredine Choukchou-Braham ◽  
Khaldoun Bachari ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Apoptotic Cell ◽  
Structural Diversity ◽  
Antibacterial Activities ◽  
Innovative Drug ◽  
Neuroprotective Effects ◽  
Cellular Division ◽  
Bioactive Natural Products ◽  
Anaplastic Lymphoma ◽  
Dna Binders

The present review deals with the progress in medicinal chemistry of spirocyclic compounds, a wider class of natural and synthetic organic molecules, defined as a hybrid of two molecular entities covalently linked via a unique tetrahedral carbon. This spiro central carbon confers to the molecules a tridimensional structurally oriented framework, which is found in many medicinally relevant compounds, a well-known example is the antihypertensive spironolactone. Various bioactive natural products possess the privileged spiro linkage and different chemo-types thereof become synthetically accessible since the 20th century. Actually, there has been a growing interest in the synthesis of heterocyclic hybrids gathered via a spiro carbon. Most of these combinations are two moieties in one scaffold being able to interfere with biological systems through sequential mechanisms. Spirocyclic hybrids containing indole or oxindole units are compounds exhibiting higher interaction with biological receptors by protein inhibition or enzymatic pathways and their recognition as promising anticancer agents in targeted chemotherapy is foreseen. These specific, low-weight and noncomplex spirocyclic hybrids are potent inhibitors of SIRT1, Mdm2–p53 and PLK4, showing affinity for anaplastic lymphoma kinase (ALK) receptor. They are also known as excellent DNA binders, acting on cellular division by arresting the cell cycle at different phases and inducing apoptotic cell death. A structural diversity of spirocyclic hybrids has proved neuroprotective effects, anti-HIV, antiviral and antibacterial activities. Hundred of papers are mentioned in this review underlying chemical issues and pharmacological potencies of spiro compounds, which render them impressive synthetic hits for innovative drug conception.

Sign in / Sign up

Export Citation Format

Share Document