scholarly journals Sequence-selective DNA binding with cell-permeable oligoguanidinium–peptide conjugates

2015 ◽  
Vol 51 (23) ◽  
pp. 4811-4814 ◽  
Author(s):  
Jesús Mosquera ◽  
Mateo I. Sánchez ◽  
Julián Valero ◽  
Javier de Mendoza ◽  
M. Eugenio Vázquez ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Peptide Binding ◽  
Peptide Fragment ◽  
Peptide Conjugates ◽  
Bzip Protein ◽  
Short Peptide ◽  
Peptide Binding Site ◽  
Selective Dna Binding

Conjugation of a short peptide fragment from a bZIP protein to an oligoguanidinium tail results in a DNA-binding miniprotein that selectively interacts with composite sequences containing the peptide-binding site next to an A/T-rich tract.

Rapid Elaboration of Fragments into Leads Applied to Bromodomain-3 Extra Terminal Domain

2020 ◽  
Author(s):  
Luke Adams ◽  
Lorna E. Wilkinson-White ◽  
Menachem J. Gunzburg ◽  
Stephen J. Headey ◽  
Martin J. Scanlon ◽  
...  
Keyword(s):  
Binding Site ◽  
Systematic Approach ◽  
Structural Information ◽  
Peptide Binding ◽  
Chemical Diversity ◽  
Chemical Probes ◽  
Protein Targets ◽  
Structure Activity ◽  
Peptide Binding Site ◽  
Selection Of

The development of low-affinity fragment hits into higher affinity leads is a major hurdle in fragment-based drug design. Here we demonstrate an approach for the Rapid Elaboration of Fragments into Leads (REFiL) applying an integrated workflow that provides a systematic approach to generate higher-affinity binders without the need for structural information. The workflow involves the selection of commercial analogues of fragment hits to generate preliminary structure-activity relationships. This is followed by parallel microscale chemistry using chemoinformatically designed reagent libraries to rapidly explore chemical diversity. Upon completion of a fragment screen against Bromodomain-3 extra terminal (BRD3-ET) domain we applied the REFiL workflow, which allowed us to develop a series of tetrahydrocarbazole ligands that bind to the peptide binding site of BRD3-ET. With REFiL we were able to rapidly improve binding affinity >30-fold. The REFiL workflow can be applied readily to a broad range of protein targets without the need of a structure, allowing the efficient evolution of low-affinity fragments into higher affinity leads and chemical probes.<br>

Solubilization and Characterization of Calcitonin Gene-Related Peptide Binding Site from Porcine Spinal Cord

1988 ◽  
Vol 50 (2) ◽  
pp. 480-485 ◽  
Author(s):  
Osamu Hiroshima ◽  
Yoshihisa Sano ◽  
Teruaki Yuzuriha ◽  
Chiyuki Yamato ◽  
Akira Saito ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Binding Site ◽  
Peptide Binding ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Binding Site

The Crystal Structures of the SH2 Domain of p56lckComplexed with Two Phosphonopeptides Suggest a Gated Peptide Binding Site

1995 ◽  
Vol 246 (2) ◽  
pp. 344-355 ◽  
Author(s):  
Vincent Mikol ◽  
Götz Baumann ◽  
Thomas H. Keller ◽  
Ute Manning ◽  
Mauro G.M. Zurini
Keyword(s):  
Binding Site ◽  
Crystal Structures ◽  
Peptide Binding ◽  
Sh2 Domain ◽  
Peptide Binding Site

Autoradiographic localization of a novel peptide binding site in rat brain using the substance P analog, eledoisin

Neuropeptides ◽  
1984 ◽  
Vol 4 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Richard B. Rothman ◽  
Janine A. Danks ◽  
Miles Herkenham ◽  
Margaret A. Cascieri ◽  
Gary G. Chicchi ◽  
...  
Keyword(s):  
Substance P ◽  
Binding Site ◽  
Rat Brain ◽  
Peptide Binding ◽  
Peptide Binding Site

Crystal structure of YrrB: A TPR protein with an unusual peptide-binding site

2007 ◽  
Vol 360 (4) ◽  
pp. 784-790 ◽  
Author(s):  
Dohyun Han ◽  
Jongkil Oh ◽  
Kyunggon Kim ◽  
Hyosun Lim ◽  
Youngsoo Kim
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Peptide Binding ◽  
Peptide Binding Site

scholarly journals Characterization of the Escherichia coli SecA Signal Peptide-Binding Site

2011 ◽  
Vol 194 (2) ◽  
pp. 307-316 ◽  
Author(s):  
L. M. Grady ◽  
J. Michtavy ◽  
D. B. Oliver
Keyword(s):  
Escherichia Coli ◽  
Binding Site ◽  
Signal Peptide ◽  
Peptide Binding ◽  
Peptide Binding Site

scholarly journals Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9

2020 ◽  
Author(s):  
D. R. Littler ◽  
B. S. Gully ◽  
R. N. Colson ◽  
J Rossjohn
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Peptide Binding ◽  
Structural Protein ◽  
Dimer Interface ◽  
X Ray ◽  
3C Protease ◽  
Peptide Binding Site ◽  
High Level ◽  
Viral Genomic Rna

AbstractMany of the proteins produced by SARS-CoV-2 have related counterparts across the Severe Acute Respiratory Syndrome (SARS-CoV) family. One such protein is non-structural protein 9 (Nsp9), which is thought to mediate both viral replication and virulence. Current understanding suggests that Nsp9 is involved in viral genomic RNA reproduction. Nsp9 is thought to bind RNA via a fold that is unique to this class of betacoronoaviruses although the molecular basis for this remains ill-defined. We sought to better characterise the SARS-CoV-2 Nsp9 protein and subsequently solved its X-ray crystal structure, in an apo-form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence (LEVL). The structure of the SARS-CoV-2 Nsp9 revealed the high level of structural conservation within the Nsp9 family. The exogenous peptide binding site is close to the dimer interface and impacted on the relative juxtaposition of the monomers within the homodimer. Together we have established a protocol for the production of SARS-CoV-2 Nsp9, determined its structure and identified a peptide-binding site that may warrant further study from the perspective of understanding Nsp9 function.

Rapid Elaboration of Fragments into Leads Applied to Bromodomain-3 Extra Terminal Domain

2020 ◽  
Author(s):  
Luke Adams ◽  
Lorna E. Wilkinson-White ◽  
Menachem J. Gunzburg ◽  
Stephen J. Headey ◽  
Martin J. Scanlon ◽  
...  
Keyword(s):  
Binding Site ◽  
Systematic Approach ◽  
Structural Information ◽  
Peptide Binding ◽  
Chemical Diversity ◽  
Chemical Probes ◽  
Protein Targets ◽  
Structure Activity ◽  
Peptide Binding Site ◽  
Selection Of

The development of low-affinity fragment hits into higher affinity leads is a major hurdle in fragment-based drug design. Here we demonstrate an approach for the Rapid Elaboration of Fragments into Leads (REFiL) applying an integrated workflow that provides a systematic approach to generate higher-affinity binders without the need for structural information. The workflow involves the selection of commercial analogues of fragment hits to generate preliminary structure-activity relationships. This is followed by parallel microscale chemistry using chemoinformatically designed reagent libraries to rapidly explore chemical diversity. Upon completion of a fragment screen against Bromodomain-3 extra terminal (BRD3-ET) domain we applied the REFiL workflow, which allowed us to develop a series of tetrahydrocarbazole ligands that bind to the peptide binding site of BRD3-ET. With REFiL we were able to rapidly improve binding affinity >30-fold. The REFiL workflow can be applied readily to a broad range of protein targets without the need of a structure, allowing the efficient evolution of low-affinity fragments into higher affinity leads and chemical probes.<br>

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