NMR-based identification of peptides that specifically recognize the d-arm of tRNA

Tisné, Carine; Guillière, Florence; Dardel, Frédéric

doi:10.1016/j.biochi.2005.02.003

Cited by 11 publications

(8 citation statements)

References 21 publications

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“…An NMR screen, based on high selectivity, was used and three short peptides were selected, one of them interacting with tRNA 3 Lys with a 2 mM dissociation constant. All three peptides were found to recognize the 3D structure of the D-stem and loop of tRNAs [152]. Compounds were further optimized for tRNA 3 Lys binding [153,154]; their effect on initiation of reverse transcription needs now to be tested.…”

Section: Initiation Of Reverse Transcription As a Drug Targetmentioning

confidence: 99%

Initiation of HIV Reverse Transcription

Isel

Ehresmann

Marquet

2010

Viruses

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Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

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Section: Initiation Of Reverse Transcription As a Drug Targetmentioning

confidence: 99%

Initiation of HIV Reverse Transcription

Isel

Ehresmann

Marquet

2010

Viruses

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“…This screening method has been automated and streamlined on an NMR spectroscopy platform, which includes a flow-injection probe and a pipetting robot to perform probe filling with sample. [13] A primary screen was performed with several cyclopentanic diamines, which are easily available on a multigram scale from meso-bicyclic hydrazines. [14] The choice of these fragments was based on the assumption that conformationally restricted 1,3-diamines could mimic the central framework of aminoglycosides, which are known to be promiscuous RNA binders.…”

Section: Resultsmentioning

confidence: 99%

Design of tRNA^Lys₃ Ligands: Fragment Evolution and Linker Selection Guided by NMR Spectroscopy

Chung

Tisné

Lecourt

et al. 2009

Chemistry A European J

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A fragment-based approach for the synthesis of ligands of tRNA(Lys) (3), the HIV reverse-transcription primer, is described. The use of NMR spectroscopy has proved to be very useful in this approach, not only to detect low-affinity complexes between small compounds and RNA, but also to provide information on their binding mode and on the way they can be connected. This NMR-spectroscopy-guided analysis enabled us to design micromolar ligands after the optimisation and connection of millimolar fragments with an appropriate linker. The influence of the linker region on the binding affinity and selectivity outlines the importance of having a flexible assemblage strategy with a variety of linkers in such an approach.

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“…However, the rational design of selective binders of tRNA Lys3 is difficult because of the lack of known ligands9 and the similarity of its shape to that of other tRNA molecules. A combinatorial approach led only to low‐affinity structure‐specific peptide ligands 10. However, the availability of crystallographic11 and NMR spectroscopic data12, 13 and of an efficient expression system made it possible to undertake a fragment‐based approach 14.…”

Section: Methodsmentioning

confidence: 99%