Click chemistry joins small reactive molecular building blocks together to drive binding reactions.

The Scripps Research Institute and Aileron Therapeutics entered an agreement that will add Scripps Research’s Click chemistry to Aileron’s stabilized peptide and protein technology platforms. The deal provides Aileron exclusive, worldwide rights to utilize Click chemistry for therapeutics and nonexclusive, worldwide rights for diagnostics.

The Click chemistries subject to this agreement were developed by Nobel Laureate K. Barry Sharpless, Ph.D., the W.M. Keck professor of chemistry at Scripps Research. Click chemistry describes synthetic chemistry tailored to generate substances quickly and reliably. This is done by joining, or clicking, small reactive molecular building blocks together selectively and covalently to drive a spontaneous and irreversible binding reaction, a process that is inspired by natural chemistry.

Click Chemistry has the potential to accelerate the drug-discovery process by utilizing a few practical and reliable reactions and by making each reaction in a multistep synthesis fast, efficient, and predictable.

“Aileron has discovered how to enable and, more importantly, where to use certain peptide and protein macrocyclization chemistries to drive therapeutic product profiles,” says Tomi Sawyer, Ph.D., CSO and svp of drug discovery and innovative technologies at Aileron. “This agreement with Scripps Research further expands our arsenal to create novel therapeutics including protein and nonhelical peptide therapeutics and will give us access to one of the top biomedical research organizations in the world.”

Aileron’s stapled peptide technology platform locks peptides into their biologically active shape by the formation of one or more stabilizing macrocycles, mimicking the structures found in nature. This process captures the best features of both small molecules and therapeutic proteins, according to Aileron. It endows the peptide with drug-like properties including efficient cell penetration, improved pharmacokinetics, high-affinity binding to large target protein surfaces, and excellent stability within the body, the firm adds.

Aileron expects stapled peptides to expand the number of druggable targets by providing an opportunity to address the thousands of intracellular protein-protein interactions that remain a challenge for functional modulation by current therapeutics. Preclinical studies have shown that the company’s stapled peptide compounds possess compelling potency, in vivo stability, and cell permeability.

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