Molecular drug targets for scabies: a medicinal chemistry perspective

2020 ◽  
Vol 12 (24) ◽  
pp. 2225-2238
Author(s):  
Wali Inam ◽  
Shelley Walton ◽  
Sheraz Khan ◽  
Wajahat Mahmood
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Proteolytic Enzymes ◽  
Hydrolytic Enzymes ◽  
Sarcoptes Scabiei ◽  
Causative Organism ◽  
Protein Protein Interactions ◽  
Scabies Mite ◽  
Nonpeptide Ligands ◽  
Global Population

Sarcoptes scabiei is a causative organism for scabies that affects an estimated global population of 300 million and remains a disease of significant concern. Recently, a number of potential drug targets were identified for scabies, including hydrolytic enzymes, inactivated paralogues of hydrolytic enzymes, inhibitors of host proteolytic enzymes and other proteins of interest. These discoveries remain confined to academic laboratories and institutions, failing to attract interest from researchers in commercial drug development. Here, we summarize the latest developments in the scabies mite biology and the drug targets that were subsequently identified, and we propose several peptide and nonpeptide ligands targeting the hot spots for protein–protein interactions. We also identify gaps in the development of ligands as inhibitors or modulators of these macromolecules.

scholarly journals Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

2017 ◽  
pp. 221-236 ◽  
Author(s):  
Alexander Goncearenco ◽  
Minghui Li ◽  
Franco L. Simonetti ◽  
Benjamin A. Shoemaker ◽  
Anna R. Panchenko
Keyword(s):  
Cancer Therapy ◽  
Protein Interactions ◽  
In Silico ◽  
Drug Targets ◽  
Protein Protein Interactions ◽  
Anti Cancer

An integrated strategy for the discovery of drug targets by the analysis of protein–protein interactions

2004 ◽  
Vol 238 (2) ◽  
pp. 119-130 ◽  
Author(s):  
John M. Peltier ◽  
Srdjan Askovic ◽  
Robert R. Becklin ◽  
Cindy Lou Chepanoske ◽  
Yew-Seng J. Ho ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Protein Protein Interactions ◽  
Integrated Strategy

scholarly journals Protein Dynamics in F-like Bacterial Conjugation

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 362
Author(s):  
Nicholas Bragagnolo ◽  
Christina Rodriguez ◽  
Naveed Samari-Kermani ◽  
Alice Fours ◽  
Mahboubeh Korouzhdehi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Protein Interactions ◽  
Drug Targets ◽  
Dynamic Models ◽  
Structural Information ◽  
Imaging Techniques ◽  
Antibiotic Resistance Genes ◽  
Protein Protein Interactions ◽  
Secretion Systems ◽  
Type Iv

Efficient in silico development of novel antibiotics requires high-resolution, dynamic models of drug targets. As conjugation is considered the prominent contributor to the spread of antibiotic resistance genes, targeted drug design to disrupt vital components of conjugative systems has been proposed to lessen the proliferation of bacterial antibiotic resistance. Advancements in structural imaging techniques of large macromolecular complexes has accelerated the discovery of novel protein-protein interactions in bacterial type IV secretion systems (T4SS). The known structural information regarding the F-like T4SS components and complexes has been summarized in the following review, revealing a complex network of protein-protein interactions involving domains with varying degrees of disorder. Structural predictions were performed to provide insight on the dynamicity of proteins within the F plasmid conjugative system that lack structural information.

Pseudokinase drug intervention: a potentially poisoned chalice

2013 ◽  
Vol 41 (4) ◽  
pp. 1083-1088 ◽  
Author(s):  
Jeroen Claus ◽  
Angus J.M. Cameron ◽  
Peter J. Parker
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Binding Pocket ◽  
Atp Binding ◽  
Potential Drug ◽  
Protein Protein Interactions ◽  
Drug Intervention ◽  
Potential Impact ◽  
Potential Drug Targets ◽  
Selection Of

Pseudokinases, the catalytically impaired component of the kinome, have recently been found to share more properties with active kinases than previously thought. In many pseudokinases, ATP binding and even some activity is preserved, highlighting these proteins as potential drug targets. In both active kinases and pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can stabilize specific conformations required for activity and protein–protein interactions. We discuss the implications of locking particular conformations in a selection of (pseudo)kinases and the dual potential impact on the druggability of these proteins.

scholarly journals Unbiased Identification of Extracellular Protein–Protein Interactions for Drug Target and Biologic Drug Discovery

2021 ◽  
Author(s):  
Shengya Cao ◽  
Nadia Martinez-Martin
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Drug Target ◽  
Drug Targets ◽  
Extracellular Protein ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Drug Target Discovery ◽  
Technological Improvements ◽  
Targeted Drug Discovery

Technological improvements in unbiased screening have accelerated drug target discovery. In particular, membrane-embedded and secreted proteins have gained attention because of their ability to orchestrate intercellular communication. Dysregulation of their extracellular protein–protein interactions (ePPIs) underlies the initiation and progression of many human diseases. Practically, ePPIs are also accessible for modulation by therapeutics since they operate outside of the plasma membrane. Therefore, it is unsurprising that while these proteins make up about 30% of human genes, they encompass the majority of drug targets approved by the FDA. Even so, most secreted and membrane proteins remain uncharacterized in terms of binding partners and cellular functions. To address this, a number of approaches have been developed to overcome challenges associated with membrane protein biology and ePPI discovery. This chapter will cover recent advances that use high-throughput methods to move towards the generation of a comprehensive network of ePPIs in humans for future targeted drug discovery.

scholarly journals Fast and accurate genome-wide predictions and structural modeling of protein-protein interactions using Galaxy

2021 ◽  
Author(s):  
Aysam Guerler ◽  
Dannon Baker ◽  
Marius van den Beek ◽  
Dave Bouvier ◽  
Nate Coraor ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Structural Models ◽  
Protein S ◽  
Structural Protein ◽  
Protein Protein Interactions ◽  
High Quality ◽  
Dipeptidyl Peptidase 4 ◽  
Genome Wide ◽  
Living Organisms

Protein-protein interactions play a crucial role in almost all cellular processes. Identifying interacting proteins reveals insight into living organisms and yields novel drug targets for disease treatment. Here, we present a publicly available, automated pipeline to predict genome-wide protein-protein interactions and produce high-quality multimeric structural models. Application of our method to the Human and Yeast genomes yield protein-protein interaction networks similar in quality to common experimental methods. We identified and modeled Human proteins likely to interact with the papain-like protease of SARS-CoV2's non-structural protein 3 (Nsp3). We also produced models of SARS-CoV2's spike protein (S) interacting with myelin-oligodendrocyte glycoprotein receptor (MOG) and dipeptidyl peptidase-4 (DPP4). The presented method is capable of confidently identifying interactions while providing high-quality multimeric structural models for experimental validation. The interactome modeling pipeline is available at usegalaxy.org.

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