scholarly journals Rational Design and Synthesis of Right-Handed d-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions

2020 ◽  
Vol 85 (16) ◽  
pp. 10552-10560
Author(s):  
Peng Sang ◽  
Yan Shi ◽  
Pirada Higbee ◽  
Minghui Wang ◽  
Sami Abdulkadir ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rational Design ◽  
Protein Protein Interactions ◽  
Design And Synthesis

scholarly journals Engineered pH-Sensitive Protein G / IgG Interaction

2020 ◽  
Author(s):  
Ramesh K. Jha ◽  
Allison Yankey ◽  
Kalifa Shabazz ◽  
Leslie Naranjo ◽  
Nileena Velappan ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Protein Design ◽  
Protein Interactions ◽  
Rational Design ◽  
Protein G ◽  
Acidic Ph ◽  
Protein Protein Interactions ◽  
Natural Interface ◽  
Complex Stimuli ◽  
Igg Purification

ABSTRACTWhile natural protein-protein interactions have evolved to be induced by complex stimuli, rational design of interactions that can be switched-on-demand still remain challenging in the protein design world. Here, we demonstrate a computationally redesigned natural interface for improved binding affinity could further be mutated to adopt a pH switchable interaction. The redesigned interface of Protein G-IgG Fc domain, when incorporated with histidine and glutamic acid on Protein G (PrG-EHHE), showed a switch in binding affinity by 50-fold when pH was altered from mild acidic to mild basic. The wild type (WT) interface only showed negligible switch. The overall binding affinity at mild acidic pH for PrG-EHHE outperformed the WT PrG interaction. The new reagent PrG-EHHE will be revolutionary in IgG purification since the traditional method of using an extreme acidic pH for elution can be circumvented.Abstract Figure

scholarly journals Bacteria Use Structural Imperfect Mimicry To Hijack The Host Interactome

2020 ◽  
Author(s):  
Natalia Sanchez de Groot ◽  
Marc Torrent Burgas
Keyword(s):  
Protein Interactions ◽  
Rational Design ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Eukaryotic Proteins ◽  
Host Pathogen ◽  
Imperfect Mimicry ◽  
The Way

ABSTRACTBacteria use protein-protein interactions to infect their hosts and hijack fundamental pathways, which ensures their survival and proliferation. Hence, the infectious capacity of the pathogen is closely related to its ability to interact with host proteins. Here, we show that hubs in the host-pathogen interactome are isolated in the pathogen network by adapting the geometry of the interacting interfaces. An imperfect mimicry of the eukaryotic interfaces allows pathogen proteins to actively bind to the host’s target while preventing deleterious effects on the pathogen interactome. Understanding how bacteria recognize eukaryotic proteins may pave the way for the rational design of new antibiotic molecules.

Rational Design of Selective Small-Molecule Inhibitors for β-Catenin/B-Cell Lymphoma 9 Protein–Protein Interactions

2015 ◽  
Vol 137 (38) ◽  
pp. 12249-12260 ◽  
Author(s):  
Logan R. Hoggard ◽  
Yongqiang Zhang ◽  
Min Zhang ◽  
Vanja Panic ◽  
John A. Wisniewski ◽  
...  
Keyword(s):  
B Cell ◽  
Small Molecule ◽  
Protein Interactions ◽  
Rational Design ◽  
Small Molecule Inhibitors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Protein Protein Interactions ◽  
Catenin B

Protein-Protein Interactions (PPIs) as an Alternative to Targeting the ATP Binding Site of Kinase

2016 ◽  
pp. 249-277
Author(s):  
Sailu Sarvagalla ◽  
Mohane Selvaraj Coumar
Keyword(s):  
Protein Interactions ◽  
In Silico ◽  
Rational Design ◽  
Kinase Activity ◽  
Hot Spot ◽  
Binding Pocket ◽  
Atp Binding ◽  
Protein Protein Interactions ◽  
Structure Based Drug Design ◽  
Atp Binding Site

Most of the developed kinase inhibitor drugs are ATP competitive and suffer from drawbacks such as off-target kinase activity, development of resistance due to mutation in the ATP binding pocket and unfavorable intellectual property situations. Besides the ATP binding pocket, protein kinases have binding sites that are involved in Protein-Protein Interactions (PPIs); these PPIs directly or indirectly regulate the protein kinase activity. Of recent, small molecule inhibitors of PPIs are emerging as an alternative to ATP competitive agents. Rational design of inhibitors for kinase PPIs could be carried out using molecular modeling techniques. In silico tools available for the prediction of hot spot residues and cavities at the PPI sites and the means to utilize this information for the identification of inhibitors are discussed. Moreover, in silico studies to target the Aurora B-INCENP PPI sites are discussed in context. Overall, this chapter provides detailed in silico strategies that are available to the researchers for carrying out structure-based drug design of PPI inhibitors.

scholarly journals Targeting protein–protein interactions by rational design: mimicry of protein surfaces

2006 ◽  
Vol 3 (7) ◽  
pp. 215-233 ◽  
Author(s):  
Steven Fletcher ◽  
Andrew D Hamilton
Keyword(s):  
Protein Interactions ◽  
Active Site ◽  
Rational Design ◽  
Considerable Progress ◽  
Biological Processes ◽  
Protein Protein Interactions ◽  
Protein Surfaces ◽  
Enzyme Active Site ◽  
Novel Therapeutics ◽  
Interfacial Areas

Protein–protein interactions play key roles in a range of biological processes, and are therefore important targets for the design of novel therapeutics. Unlike in the design of enzyme active site inhibitors, the disruption of protein–protein interactions is far more challenging, due to such factors as the large interfacial areas involved and the relatively flat and featureless topologies of these surfaces. Nevertheless, in spite of such challenges, there has been considerable progress in recent years. In this review, we discuss this progress in the context of mimicry of protein surfaces: targeting protein–protein interactions by rational design.

ChemInform Abstract: Design and Synthesis of Thienylpyridyl Garlands as Non-Peptidic Alpha Helix Mimetics and Potential Protein-Protein Interactions Disruptors.

ChemInform ◽  
2011 ◽  
Vol 42 (52) ◽  
pp. no-no
Author(s):  
Marcella De Giorgi ◽  
Anne Sophie Voisin-Chiret ◽  
Jana Sopkova-de Oliveira Santos ◽  
Filomena Corbo ◽  
Carlo Franchini ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Alpha Helix ◽  
Protein Protein Interactions ◽  
Design And Synthesis ◽  
Helix Mimetics

scholarly journals Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein–Protein Interactions

2020 ◽  
Vol 63 (21) ◽  
pp. 13187-13196
Author(s):  
Yan Shi ◽  
Peng Sang ◽  
Junhao Lu ◽  
Pirada Higbee ◽  
Lihong Chen ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rational Design ◽  
Protein Protein Interactions

scholarly journals Design and Synthesis of a New Orthogonally Protected Glutamic Acid Analog and Its Use in the Preparation of High Affinity Polo-like Kinase 1 Polo-box Domain – binding Peptide Macrocycles

2021 ◽  
Author(s):  
David Hymel ◽  
Kohei Tsuji ◽  
Robert A. Grant ◽  
Ramesh M. Chingle ◽  
Dominique L. Kunciw ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Binding Peptide ◽  
Design And Synthesis ◽  
High Affinity ◽  
Acid Analog ◽  
Therapeutic Development

Targeting protein – protein interactions (PPIs) has emerged as important area of discovery for anticancer therapeutic development. In the case of phospho-dependent PPIs, such as the polo-like kinase 1 (Plk1)...

Sign in / Sign up

Export Citation Format

Share Document