Abstract

In this publication attention is given to a retracted article in Science at the end of 1990 concerning the HIV-1 inhibition by a modified backbone DNA as the phosphatemethylated DNA. A disproportion in the presented data resulted in a faulty generalization of the (bio)chemical characteristics of the phosphatemethylated DNA (18- and 20-nucleotides). In the confusion and the outside pressure a related study in Nucleic Acids Research on the in vitro dynamics of a regiospecific inhibition of DNA duplication with long (20- and 18-nucleotides) and short (8-nucleotides) phosphatemethylated DNA was completely ignored. A restoration will be given based on a comprehensive view demonstrating the unique molecular and conformational properties of phosphatemethylated DNA in their (bio)chemistry towards natural DNA and RNA (HIV-1 RNA loops).

Highlights

  • After the publication in Science entitled Inhibition of HIV-1 Infectivity by Phosphate-Methylated DNA: Retraction of Moody et al [1] a number of articles have been published in order to reduce the imbalance between the various passages in the Retraction and the “meltdown” of the bio- and physical chemical properties of phosphatemethylated DNA [2]-[6]

  • The correctness of the synthetic part of the Technical Comment obtains a doubtful or negative assessment with the quote: “This result contrasts with earlier statements that the degree of phosphate-methylation of tested DNA was 90% to 100%”

  • It should be assigned that we are dealing with a high selectivity and enhanced duplex formation of phosphatemethylated DNA for its complementary natural DNA (A- and B-conformation) which is in sharp contrast with the poor hybridization affinity at the RNA level (A-conformation)

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Summary

Introduction

After the publication in Science entitled Inhibition of HIV-1 Infectivity by Phosphate-Methylated DNA: Retraction of Moody et al [1] a number of articles have been published in order to reduce the imbalance between the various passages in the Retraction (presented as a Technical Comment) and the “meltdown” of the bio- and physical chemical properties of phosphatemethylated DNA [2]-[6]. (2015) Retracted HIV Study Provides New Information about the Status of the in Vitro Inhibition of DNA Replication by Backbone Methylation. Buck degree of methylation of the 20-nucleotide DNA’s. These results conflict with their achievement in the in vitro regiospecific inhibition of DNA duplication with long and short fragments, prepared in a similar manner as in the HIV-study [7]. The suppression of the DNA polymerase I (Klenow fragment) in the inhibition experiments with the neutrally backbone-modified DNA’s as inhibitors, has been explicitly demonstrated and may be considered as an additional support for the synthesis of the methylated DNA backbones [7]

Methods and Materials
Inhibition of DNA Duplexation by Phosphatemethylated Oligodeoxynucleotides
General Remarks Concerning the Duplication Study
Conclusion
Full Text
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