Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition
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TLDR
The first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions showed enhanced cellular uptake along with modest in vivo activity.About:
This article is published in Bioorganic & Medicinal Chemistry Letters.The article was published on 2011-03-01 and is currently open access. It has received 99 citations till now. The article focuses on the topics: MDMX & Peptide.read more
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The Future of Peptide‐based Drugs
TL;DR: The suite of currently used drugs can be divided into two categories - traditional'small molecule' drugs with typical molecular weights of 5000 Da that are not orally bioavailable and need to be delivered via injection as mentioned in this paper.
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Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes
TL;DR: A new classification of peptidomimetics (classes A–D) is introduced that enables a clear assignment of available approaches for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.
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Multifaceted roles of disulfide bonds. Peptides as therapeutics.
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Peptide stapling techniques based on different macrocyclisation chemistries
TL;DR: This tutorial review categorise and analyse key examples of peptide stapling in terms of their synthesis and applicability to biological systems.
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Modulators of Protein-Protein Interactions
TL;DR: This research presents a novel and scalable approaches called “Smart Gene Regulation” that allows for real-time annotation of the FISH signal in the Eindhoven–Borff–Seiden cellular automaton.
References
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Journal ArticleDOI
Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features
Wolfgang Kabsch,Chris Sander +1 more
TL;DR: A set of simple and physically motivated criteria for secondary structure, programmed as a pattern‐recognition process of hydrogen‐bonded and geometrical features extracted from x‐ray coordinates is developed.
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p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
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Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain.
Paul H. Kussie,Svetlana Gorina,Vincent Marechal,Brian Elenbaas,Jacque Moreau,Arnold J. Levine,Nikola P. Pavletich +6 more
TL;DR: The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-Residue transactivation domain peptide of p53 revealed that MDM 2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic α helix, supporting the hypothesis thatMDM2 inactivates p53 by concealing its transactivationdomain.
Journal ArticleDOI
The p53-mdm-2 autoregulatory feedback loop
TL;DR: The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm -2 gene can be regulated by the level of wild-type p53 protein.
Journal ArticleDOI
Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.
Michael Sattler,Heng Liang,David G. Nettesheim,Robert P. Meadows,John E. Harlan,Matthias Eberstadt,Ho Sup Yoon,Suzanne B. Shuker,Brian S. Chang,Andy J. Minn,Craig B. Thompson,Stephen W. Fesik +11 more
TL;DR: The structure and binding affinities of mutant Bak peptides indicate that the Bak peptide adopts an amphipathic α helix that interacts with Bcl-xL through hydrophobic and electrostatic interactions.
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