Synthesis of Structurally Simplified Aureolic Acid Aglycone-C-D-E Trisaccharide Analogues

2002 ◽  
Vol 55 (2) ◽  
pp. 113 ◽  
Author(s):  
W. R. Roush ◽  
N. A. Powell ◽  
R. A. James

Syntheses of aureolic acid analogues (5) and (6) with (2S)- and (2R)-acyloin stereochemistry, respectively, are described. The synthesis of (5) utilizes a `C + DE' glycosidation sequence, whereas analogue (6), with unnatural (2R)-acyloin stereochemistry, was synthesized by a sequence in which the entire C-D-E trisaccharide was introduced in a single step. While these syntheses provided sufficient quantities of the two aureolic acid analogues for use in studies of Mg2+ complex formation and deoxyribonucleic acid (DNA) binding, this work also highlights certain limitations in the use of 2-thiophenyl glycosyl donors for synthesis of 2-deoxy-β-glycosides. Specifically, difficulties were encountered in the identification of a protecting group for the aglycone C8 phenol that is fully compatible with the conditions required for reductive removal of the thiophenyl substituents after completion of the glycosidation sequence. Sensitivity of the C2 acyloin stereocentre to the conditions required for deprotection of a phenolic acetate ester are also highlighted in the syntheses of (5), and especially of (6).

1999 ◽  
Vol 274 (18) ◽  
pp. 12765-12773 ◽  
Author(s):  
Liliane A. Dickinson ◽  
John W. Trauger ◽  
Eldon E. Baird ◽  
Peter B. Dervan ◽  
Barbara J. Graves ◽  
...  

1992 ◽  
Vol 12 (2) ◽  
pp. 444-454
Author(s):  
S M Ruben ◽  
R Narayanan ◽  
J F Klement ◽  
C H Chen ◽  
C A Rosen

The NF-kappa B transcription factor complex is composed of two proteins, designated p50 and p65, both having considerable homology to the product of the rel oncogene. We present evidence that the p65 subunit is a potent transcriptional activator in the apparent absence of the p50 subunit, consistent with in vitro results demonstrating that p65 can interact with DNA on its own. To identify the minimal activation domain, chimeric fusion proteins between the DNA binding domain of the yeast transcriptional activator protein GAL4 and regions of the carboxy terminus of p65 were constructed, and their transcriptional activity was assessed by using a GAL4 upstream activation sequence-driven promoter-chloramphenicol acetyltransferase fusion. This analysis suggests that the boundaries of the activation domain lie between amino acids 415 and 550. Moreover, single amino acid changes within residues 435 to 459 greatly diminished activation. Similar to other activation domains, this region contains a leucine zipper-like motif as well as an overall net negative charge. To identify those residues essential for DNA binding, we made use of a naturally occurring derivative of p65, lacking residues 222 to 231 (hereafter referred to as p65 delta), and produced via an alternative splice site. Gel mobility shift analysis using bacterially expressed p65, p65 delta, and various mutants indicates that residues 222 to 231 are important for binding to kappa B DNA. Coimmunoprecipitation analysis suggests that these residues likely contribute to the multimerization function required for homomeric complex formation or heteromeric complex formation with p50 in that no association of p65 delta with itself or with p50 was evident. However, p65 delta was able to form weak heteromeric complexes with p65 that were greatly reduced in their ability to bind DNA. On the basis of these findings, we suggest that subtle changes within the proposed multimerization domain can elicit different effects with the individual Rel-related proteins and that a potential role of p65 delta may be to negatively regulate NF-kappa B function through formation of nonfunctional heteromeric complexes.


PEDIATRICS ◽  
1965 ◽  
Vol 36 (5) ◽  
pp. 714-720
Author(s):  
Joseph L. Potter ◽  
LeRoy W. Matthews ◽  
Samuel Spector ◽  
Joy Lemm

1. Complex formation and precipitation of DNA by neomycin, with consequent inactivation of the antibiotic, has been shown to occur in the pulmonary secretions of patients with cystic fibrosis. 2. Highly polymerized DNA from a variety of sources, as well as two samples of RNA, were precipitated by neomycin in vitro. Polymixin, kanamycin, colymycin, and streptomycin similarly co-precipitate with DNA in vitro. 3. The minimum chain length of polynucleotide required for precipitation in the DNA-neomycin system was 10. 4. The complex is readily attacked by DNase I resulting in the splitting of the DNA and the liberation of the antibiotic. Both components of the complex are solubilized in M sodium chloride. 5. The resistance of purulent foci of infection to therapy with basic antimicrobial agents may, in part, be due to the complex formation with the high levels of DNA found at the site of infection.


2019 ◽  
Vol 43 (17) ◽  
pp. 6702-6711 ◽  
Author(s):  
Hongqin Yang ◽  
Qingle Zeng ◽  
Ze He ◽  
Di Wu ◽  
Hui Li

The binding interaction of niraparib (MK-4827), a poly(ADP-ribose) polymerase inhibitor, with calf thymus deoxyribonucleic acid (ctDNA) has been explored by various theoretical and experimental techniques.


2020 ◽  
Vol 85 (24) ◽  
pp. 16166-16181
Author(s):  
Nahoko Yagami ◽  
Amol M. Vibhute ◽  
Hide-Nori Tanaka ◽  
Naoko Komura ◽  
Akihiro Imamura ◽  
...  

The Analyst ◽  
2014 ◽  
Vol 139 (9) ◽  
pp. 2193-2198 ◽  
Author(s):  
Yun Zhang ◽  
Fang Liu ◽  
Jinfang Nie ◽  
Fuyang Jiang ◽  
Caibin Zhou ◽  
...  

This paper describes for the first time an electrochemical biosensor, which employs a DNA probe modified with a redox tag close to electrode surface, for picomolar detection of a sequence-specific DNA-binding protein.


2011 ◽  
Vol 39 (4) ◽  
pp. 3853-3861 ◽  
Author(s):  
Soheila Kashanian ◽  
Mohammad Mehdi Khodaei ◽  
Parvaneh Pakravan ◽  
Hadi Adibi

Sign in / Sign up

Export Citation Format

Share Document