Guiding Transient Peptide Assemblies with Structural Elements Around Abiotic Phosphate Fuels

Biochemical energy carriers, such as triphosphates (ATP, GTP) drive selective processes, by incorporating chemical information (Adenine vs. Guanine) in their structure. These recognition elements match with complex machineries through a variety of non-covalent interactions, enabling specific targeting of functions. In contrast, most approaches in non-equilibrium systems do not consider the structure of the fuel as a critical element to control the processes. Herein, we show that the amino acid side chains (A, F, Nap) in the structure of activated aminoacyl phosphate esters can direct assembly and reactivity in the context of non-equilibrium structure formation. We focus on the ways in which the activated amino acids guide structure formation and how structures and reactivity cross regulate when constructing different assemblies. Through the chemical functionalization of energy-rich aminoacyl phosphate esters, we are able to control the coupling yield to esters and thioesters upon adding dipeptides containing tyrosine or cysteine amino acid residues. The structural elements around the phosphate esters guide the lifetime of the structures formed and their supramolecular assemblies, which can further be influenced by the structure and reactivity of dipeptide substrates. Moreover, we demonstrate that an aminoacyl phosphate ester incorporating a tyrosine residue (Y) can autonomously generate a pool of high energy molecules, where dynamic oligomerization and de-oligomerization of esters occurs in a single step process. These findings suggest that activated amino acids with varying reactivity and energy contents can pave the way for designing and fabricating structured fuels