Non-canonical Amino Acids for in vitro Display Systems

AstraZeneca aims to build a world class peptide discovery platform, combining **phage and mRNA display****technologies and amenable to the incorporation of a wide variety of non-canonical amino acids** (ncAAs) in those display systems, from ncAAs capable of forming covalent bonds to enable new chemistries in peptides, such as cyclization, to ncAAs which can introduce novel physicochemical properties, such as altered hydrophobicity, charge, or backbone rigidity, to manipulate peptide solubility, cellular uptake, or overall structural dynamics.

The team at AstraZeneca is seeking solutions for the efficient incorporation of ncAAs in phage and/or mRNA display systems that allow for thioether macrocycle cyclisation and/or efficient incorporation of a range of amino acids. Proposed solutions to this challenge should meet the following solution requirements to be considered for funding by AstraZeneca. The selected collaborator will need to provide AstraZeneca with reagents allowing for at least one of the following: 

• Efficient incorporation of ncAAs allowing for thioether macrocycle cyclisation in a phage display system. This should go beyond the simple use of evolved tRNA synthetases and overcome some of the limitations of stop codon reprogramming
• Efficient incorporation of ncAAs allowing for thioether macrocycle cyclisation in an mRNA display/cell free protein expression system
• Incorporation of other types of ncAA such as but not limited to N-methylated amino acids, fluorosulphate-amino acid, Aib, in an mRNA display/cell free protein expression system

Submission InformationAstraZeneca invites applications from both academic and biotech organizations. Applicants should complete the submission form [ADD LINK] which should contain a brief, non‑confidential overview of your proposal, demonstrating how the RFP requirements are satisfied by your approach. Proposals should outline the resources required to solve the problem. Additional submission requirements are highlighted on page [NUMBER] of the submission form. To submit your proposal, please visit our website, register, and submit your application form under the appropriate Connect campaign.