We chose a chemically fueled, dynamic covalent bond between the ester of a peptide's C-terminus and a tyrosine's phenol. In aqueous media, an ester will not form spontaneously but requires an activating agent (fuel-driven activation). Moreover, it will hydrolyze spontaneously (deactivation). Specifically, we work with the peptide motif Ac-X-Y-XX-D-OH, in which Y stands for tyrosine and carries the phenol side group, D means aspartic acid, and X being either glycines, arginines, alanines, phenylalanine or tryptophan to direct the self-assembly of the peptides (Scheme 1B). In previous work, we have demonstrated that C-terminal aspartic acid easily converts into its corresponding anhydride by reaction with carbodiimides like EDC. One carboxylate is first activated by EDC and the O-acylurea is converted by an intramolecular attack of the second carboxylate group. The anhydride is hydrolytically unstable, so it has a limited lifetime in aqueous media. Depending on the structure of the starting material, transient vesicles, fibres, or complex coacervates were accessible with this chemical reaction cycle. By applying dicarboxylates that were derived from succinic acid with long alkyl or alkenyl tails, dynamic emulsions could be formed that could even be applied as drug delivery platforms. We hypothesized that a tyrosine's phenol as a nucleophile would react with such anhydrides to form an intermolecular phenol ester. The resulting ester contains a C-terminal aspartic acid and a free tyrosine and can thus continue the process. Put differently, a monomer can react with fuel to be dimerized, after which it can further react to make trimers and further oligomers. Besides, all peptides can also form intramolecular esters corresponding to the cyclic monomer, dimer, and oligomers. Finally, because of the hydrolytically labile nature of phenol esters, all library members are transient and will decay to their monomer state unless constantly supplied with fuel. We tested the simplest library member possible, Ac-YGGD-OH, in which G stands for glycine, the smallest natural amino acid (Fig. ). We used 3 mM of peptide in 200 mM MES at pH 5.3. We applied 10 mM of the chemical fuel and, after 45 minutes, analyzed the outcome of the chemical reaction cycle using HPLC (Figure ). Excitingly, we observed around 15 new peaks in the chromatogram, demonstrating that the dynamic combinatorial library produces an abundance of new species. By mass spectrometry, we identified the molecular weights corresponding to the cyclic monomer, linear dimer, cyclic dimer, and linear trimer (see SI for details). Noteworthy, potential isomers with the same molecular weight exist in this dynamic combinatorial library. For example, a linear trimer has the same molecular weight as a branched dimer, while a cyclic trimer has the same molecular weight as a cyclic dimer with a branch. This combinatorial explosion explains the high number of product peaks in a chromatogram. Nevertheless, these new species were dynamically evolving until, after roughly 15 hours, the last peak had completely decayed. The decay of all peaks implies that all the new library members formed in response to fuel were transient.