PMID: 11931614Apr 5, 2002Paper

Novel approach for linking genotype to phenotype in vitro by exploiting an extremely strong interaction between RNA and protein

Journal of Medicinal Chemistry
Satoshi FujitaKazunari Taira

Abstract

We recently isolated an aptamer that binds to the Tat protein of HIV-1 with extremely high affinity and specificity (Yamamoto, R.; et al. Genes Cells 2000, 5, 371.). In the present study, we exploited this strong binding to develop a novel coupling method that links genotype with phenotype. To strengthen the original RNA-protein interaction still further, we connected three units of the aptamer in tandem and three units of a peptide derived from Tat that interacted with the aptamer. The binding of the resultant RNA, which consisted of three units of the aptamer, to the resultant peptide, which consisted of three units of the peptide, was extremely strong. In fact, the RNA-protein interaction was one of the strongest ever reported, with an apparent K(d) below 16 pM. This strong interaction was attempted for the selection of functional proteins, namely, dihydrofolate reductase (DHFR) or streptavidin, which we chose as an example, and we succeeded in the expected selection, although to a limited extent, of the target protein. The noncovalent but strong interaction described above should be useful as a novel tool for the future selection of functional proteins from pools of random sequences of amino acids.

References

Jan 1, 1988·Journal of Medicinal Chemistry·K Taira, S J Benkovic
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·L C MattheakisW J Dower
Mar 14, 1996·Nature·K HaradaA D Frankel
Nov 29, 1996·Science·S B ShukerS W Fesik
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·S FujitaK Taira
Mar 17, 1997·Biochemical and Biophysical Research Communications·G M GersukR L Vessella
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·J Hanes, A Plückthun
Jun 1, 1997·Nature Biotechnology·E T Boder, K D Wittrup
Apr 1, 1996·Nature Biotechnology·J C Moore, F H Arnold
Jul 14, 1998·Nature Biotechnology·D S Tawfik, A D Griffiths
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·J HanesA Plückthun
Jan 29, 2000·Journal of Immunological Methods·C SchaffitzelA Plückthun
Apr 5, 2001·Nature·A D Keefe, J W Szostak
Apr 1, 1997·Chemical Reviews·George P. Smith, Valery A. Petrenko
Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·W P Jencks

❮ Previous
Next ❯

Citations

Jul 20, 2006·Pharmaceutical Research·Yutaka Ikeda, Kazunari Taira
Feb 21, 2003·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christian FermérMats Larhed
Apr 20, 2004·Assay and Drug Development Technologies·Simon Delagrave, Dennis J Murphy
Jun 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Scott Baskerville, David P Bartel
Oct 26, 2006·Journal of Drug Targeting·Atsushi InoueKazunari Taira
Jan 29, 2005·Chembiochem : a European Journal of Chemical Biology·Satoshi FujitaKazunari Taira

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.