The Search for Covalently Ligandable Proteins in Biological Systems.

Syed Badshah,Yahia Mabkhot

doi:10.3390/molecules21091170

Abstract

This commentary highlights the recent article published in Nature, June 2016, titled: “Proteome-wide covalent ligand discovery in native biological systems”. They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here.

Highlights

The role of medicinal compounds that bound in covalent fashion such as penicillin, aspirin, and proton pump inhibitors are still playing their part in benefiting humankind [1]
The widespread human proteome kinases have been targeted by covalent inhibitors [10], and medicinal chemists have been working on targeting the overall proteome
They took on the daunting challenge of searching for covalent ligands using the fragment-based ligand discovery (FBLD) method

Summary

Introduction

The role of medicinal compounds that bound in covalent fashion such as penicillin, aspirin, and proton pump inhibitors are still playing their part in benefiting humankind [1]. The side effects of covalent drug inhibitors can be controlled through selective measures such as better designing and considering proper electrophilic properties of the medicinal compounds [1]. Backus et al (2016) of the Scripps Research Institute, CA, USA, published an article in Nature in which they quantitatively checked parts of small molecules that are reactive to cysteines of the thousands of proteins from the human proteome and cells [11].

Results

Conclusion