Protein Modulation Helps Drug Design Get a Grip

May 11, 2020 | Biotechnology

Fresh from GEN – Genetic Engineering and Biotechnology News, here is a noteworthy Bio Tech article for you:

In protein-protein interactions (PPIs), the participating proteins may have more activity, or less, depending on whether they have undergone a modification of some kind. The modification may be one that has been introduced deliberately, in which case its purpose is likely therapeutic. In fact, most protein-based pharmaceuticals derive their therapeutic effect from some sort of modification.

Assessing the effects of deliberate modifications is crucial to the design and selection of lead molecules for future therapeutics. Major research and commercial efforts are focused on evaluating structural modifications that activate, inhibit, or stabilize proteins, and proteins of all kinds are of interest—enzymatic kinases, proteases, transcription factors, and so on.

As you might expect, the methods used to introduce and evaluate protein modifications are varied. They are also becoming more precise, turning PPIs into frameworks for pharmaceutical analysis and the realization of efficacious therapeutics. The methods highlighted in this article demonstrate that investigators are working at multiple levels. Some investigators are developing chemical “warheads” to target varied amino acid residues; some are pairing proteins with protein fragments via molecular “tethers”; and some are integrating biophysical and functional approaches in their work. In every instance, the goal is to find “druggable” features in seemingly unpromising molecular landscapes.

A target-rich PPI environment

Maurizio Pellecchia, PhD, professor of biomedical sciences at the UC Riverside and director of UC Riverside’s Center for Molecular and Translational Medicine, is developing agents that target amino acids besides cysteine (Cys)—lysine (Lys), tyrosine (Tyr), and histidine (His)—to make more potent irreversible PPI antagonists... Read the entire article at the GEN – Genetic Engineering and Biotechnology News Blog.

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