Design von β‐Haarnadel‐Peptidmimetika zur Hemmung der Bindung des α‐helicalen HIV‐1‐Rev‐Proteins an das Rev‐RNA‐Erkennungselement

Moehle, Kerstin; Athanassiou, Zafiria; Patora, Krystyna; Davidson, Amy; Varani, Gabriele

doi:10.1002/ange.200702801

Cited by 14 publications

(7 citation statements)

References 19 publications

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“…[15,16] A d-Pro-l-Pro motif was used as a turn mimetic to give biologically active peptides a defined conformation. [17] Numerous dipeptide mimetics are known for b-hairpins, forming a b-turn and inducing or stabilizing the hairpin fold, such as Hot = Tap, which even can mediate a protein-protein interaction. [18] In this work we describe the transfer of stabilizing interactions in a model hairpin structural motif to a biologically active filaggrin sequence.…”

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confidence: 99%

Filaggrin Peptides with β‐Hairpin Structure Bind Rheumatoid Arthritis Antibodies

Fischer

Geyer

2014

Angew Chem Int Ed

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In the early detection of rheumatoid arthritis (RA) synthetic filaggrin peptides serve as antigens for rheumatoid-specific autoantibodies (anti-citrullinated peptide antibody, ACPA) in ELISA tests. In this work we present a peptide that exhibits the binding epitope of ACPA in the form of a stable folding β-hairpin. The homogeneity of the peptide folding was confirmed by NMR spectroscopy and might lead to the first proposed structure of the antibody-bound conformation of the epitope.

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confidence: 99%

Filaggrin Peptides with β‐Hairpin Structure Bind Rheumatoid Arthritis Antibodies

Fischer

Geyer

2014

Angew Chem Int Ed

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“…Recently, compounds that bind specifically to certain hairpin structures have been introduced. [13,14] After screening peptide libraries, Davies and Arenz [15] identified a compound that was able to achieve control over dicer processing of shRNAs. In addition, naturally occurring, functional RNAs have been engineered to fulfil novel tasks.…”

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confidence: 99%

Inhibition of Dicing of Guanosine‐Rich shRNAs by Quadruplex‐Binding Compounds

et al. 2008

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RNA interference is triggered by small hairpin precursors that are processed by the endonuclease dicer to yield active species such as siRNAs and miRNAs. To regulate the RNAi-mediated suppression of gene expression, we imagined a strategy that relies on the sequence-specific inhibition of shRNA precursor processing by immediate RNA-small molecule interactions. Here, we present a first step in this direction by augmenting shRNAs with guanosine-rich sequences that are prone to fold into four-stranded structures. The addition of small molecules that selectively bind to such quadruplex sequences should allow for the specific inhibition of dicing of shRNAs that contain suitable G-rich elements. In an attempt to find compounds that protect against dicer processing, we have examined the effects of quadruplex-binding compounds on the dicer processing of shRNAs containing G-quadruplexes. Although a variety of small molecules that are known to bind to quadruplexes inhibited in vitro dicing of shRNAs, only two substance classes, namely certain porphyrazines and bisquinolinium compounds, showed selective inhibition of G-rich shRNAs compared to control sequences lacking guanine-rich elements. The G-rich shRNAs displayed a potent knockdown of gene expression in mammalian cell culture, but the effect was not influenced by addition of the respective quadruplex-binding compounds.

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“…Indeed, much bulkier bsheet and zinc-finger peptides have been used previously to target RRE. [43,44] Hence, electrostatic clashes between the crosslinked peptides and the negatively charged phosphate backbone seemed an unlikely cause for the low binding affinities of Rev Figure 2). Quantum mechanical calculations at the B3LYP 6-31 + G** level were run to parameterise the azobenzene linker for subsequent MD studies (Supporting Information).…”

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confidence: 96%