While D-B-A systems to induce and follow PT across biomolecules are non-existent, their equivalent for electron transfer (ET) has been known for decades . To promote ET, an artificial light-triggered electron donor/acceptor can be introduced to a model system, thus creating a redox potential difference across the biomolecule upon excitation (Fig ). An analogous system to promote PT requires a light-triggered alteration in ΔpKa as the PMF for the PT process between donor (D) and acceptor (A), bridged by a biomolecule (Fig. ). This is the governing mechanism of our new system that is based on molecular photoacids (PAs) and photobases (PBs) as D and A, respectively. PAs and PBs are capable of excited-state proton transfer or capture, respectively, stemming from a fundamental difference in pKa values between their electronic ground-state and excited-state . In this study, we chose 7-hydroxycoumarinyl-4-acetic acid (7HC) as the PA D and 6-aminoquinoline (6AQ) as the PB A, respectively (Fig. ), which were designed to have similar excitation energies to initiate the PT process in a controlled manner . Upon excitation, the acid-base properties of PAs and PBs are altered, resulting in a giant excited-state pKa gap (ΔpKa * >11, see below), which serves as the PMF for the PT across the bridge (Fig. ). Here, we synthesized unnatural amino acids (UAAs) containing the PA and PB, thus enabling the use of solid-phase peptide synthesis (SPPS) to incorporate the proton D and A at desired positions within peptides. For the first exploration of our system, we chose to synthesize peptides that differ in their amino acid composition, comparing the hydrophobic Ala residue to the titratable oxoamino-acid of Glu. To synthesize the UAAs, we covalently attached 7HC and 6AQ to the side chain of Fmoc-Lys(OMe)-NH2 and Fmoc-Glu(OtBu)-COOH, respectively (Schemes S1-4). The final UAA versions of D and A are Lys-7HC and Glu-6AQ, respectively (SI section 2). Following the synthesis of the UAAs, the D-B-A systems were synthesized using SPPS (Schemes S6 and S7). We synthesized two peptide bridges for this study (Fig. ): (Glu-Ala)4 ((EA)4) and Ala8 ((A)8), both in the presence and absence of the A; D-B-A and D-B configurations. As stated, the bridges were chosen based on the involvement of titratable oxo-amino-acids in PT, while hydrophobic or nonpolar side chains might hinder the process . In the design, Ala was placed at alternate positions to Glu to achieve a helical secondary structure suitable for the study.