2-Amino-1,8-naphthyridine Dimer (ANP77), a High-Affinity Binder to the Internal Loops of C/CC and T/CC Sites in Double-Stranded DNA

Author(s):  
Bimolendu Das ◽  
Konami Nagano ◽  
Gota Kawai ◽  
Asako Murata ◽  
Kazuhiko Nakatani
1991 ◽  
Vol 173 (2) ◽  
pp. 287-296 ◽  
Author(s):  
R Shefner ◽  
G Kleiner ◽  
A Turken ◽  
L Papazian ◽  
B Diamond

We have characterized four IgG monoclonal antibodies (mAbs) derived from BALB/c mice that bind double-stranded DNA (dsDNA) with high affinity. The hydridomas were selected for expression of a member of the VHS107 family. Three of the four cell lines use the VH11 gene and one uses the VH1 gene. These antibodies exhibit many characteristics of pathogenic anti-DNA antibodies. They are high affinity and not broadly crossreactive. Unlike the anti-DNA antibodies in autoimmune mice, they exhibit no somatic mutation in their VH genes. These results demonstrate that somatic mutation of VHS107 genes is not necessary for generating high affinity dsDNA binding. The fact that such antibodies have not previously been reported suggests that they are rare and that their expression may be downregulated in both nonautoimmune and autoimmune individuals.


2020 ◽  
Vol 208 ◽  
pp. 111090
Author(s):  
Romana Masnikosa ◽  
Milan M. Milutinović ◽  
Ivo Crnolatac ◽  
Aleksandar Tot ◽  
Suzana Veličković ◽  
...  

1990 ◽  
Vol 269 (3) ◽  
pp. 679-684 ◽  
Author(s):  
Z H Abraham ◽  
N Symonds

Recombinant Mu gam gene protein (Mu GAM) synthesized in Escherichia coli accumulates in the form of insoluble inclusion bodies which, after cell lysis and low-speed centrifugation, can be recovered in the pellet fraction. This property was utilized in a purification procedure for Mu GAM based on guanidine hydrochloride denaturation-renaturation followed by a single DEAE-cellulose chromatographic step. The purified Mu GAM was shown by nitrocellulose-filter-binding experiments to bind with high affinity to linear double-stranded DNA and more weakly to supercoiled and single-stranded forms. Mu GAM protects linear DNA from degradation by a variety of exonucleases, but only weakly inhibits endonuclease activity. These results are in accord with a model of Mu GAM conferring protection from exonuclease activity by binding to the ends of DNA.


2010 ◽  
Vol 192 (5) ◽  
pp. 321-329 ◽  
Author(s):  
Jing Geng ◽  
Peng Yuan ◽  
Chun Shao ◽  
Sheng-Bing Yu ◽  
Bo Zhou ◽  
...  

2016 ◽  
Vol 17 (11) ◽  
pp. 3609-3618 ◽  
Author(s):  
Marco Deiana ◽  
Bastien Mettra ◽  
Katarzyna Matczyszyn ◽  
Delphine Pitrat ◽  
Joanna Olesiak-Banska ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Eriks Rozners

Peptide nucleic acid (PNA) has become an extremely powerful tool in chemistry and biology. Although PNA recognizes single-stranded nucleic acids with exceptionally high affinity and sequence selectivity, there is considerable ongoing effort to further improve properties of PNA for both fundamental science and practical applications. The present paper discusses selected recent studies that improve on cellular uptake and binding of PNA to double-stranded DNA and RNA. The focus is on chemical modifications of PNA's backbone and heterocyclic nucleobases. The paper selects representative recent studies and does not attempt to provide comprehensive coverage of the broad and vibrant field of PNA modification.


Biologics ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 41-60
Author(s):  
Hanna Harant ◽  
Siegfried Höfinger ◽  
Franz Kricek ◽  
Christine Ruf ◽  
Zsolt Ruzsics ◽  
...  

The peptide TAT-I24, composed of the 9-mer peptide I24 and the TAT (48-60) peptide, exerts broad-spectrum antiviral activity against several DNA viruses. The current model of the mode of action suggests a reduction of viral entry and also a possible interaction with the viral DNA upon virus entry. To further support this model, the present study investigates the DNA binding properties of TAT-I24. DNA binding was analysed by gel retardation of a peptide-complexed DNA, fluorescence reduction of DNA labelled with intercalating dyes and determination of binding kinetics by surface plasmon resonance. Molecular dynamics simulations of DNA-peptide complexes predict high-affinity binding and destabilization of the DNA by TAT-I24. The effect on viral DNA levels of infected cells were studied by real-time PCR and staining of viral DNA by bromodeoxyuridine. TAT-I24 binds double-stranded DNA with high affinity, leading to inhibition of polymerase binding and thereby blocking of de novo nucleic acid synthesis. Analysis of early steps of virus entry using a bromodeoxyuridine-labelled virus as well as quantification of viral genomes in the cells indicate direct binding of the peptide to the viral DNA. Saturation of the peptide with exogenous DNA can fully neutralize the inhibitory effect. The antiviral activity of TAT-I24 is linked to its ability to bind DNA with high affinity. This mechanism could be the basis for the development of novel antiviral agents.


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