In protein modification through redox processes by photocatalysts, an electron transfers from a substrate to an excited photocatalyst (Scheme 4A, 4B). This electron transfer results in oxidation of the substrate while the photocatalyst is reduced (cat -). Chemical modification of proteins can be achieved at the α-position of the C-terminus, the β-position of Trp residues, and the methyl group of Met residues as details are described in the following paragraphs. In these instances, it was proposed that radicals formed on the protein are captured by Michael acceptors. Namely, the radical intermediates receive an electron from the photocatalyst in its reduced state, forming bonds as the photocatalyst returns to its ground state. The C-terminus can be preferentially reduced via a singleelectron process at a lower potential compared to the carboxylates of aspartic acid (Asp) or glutamic acid (Glu) in proteins (E1/2 red : ~1.25 V for Asp, Glu; ~0. 95 ethylidenemalonate and 3-methylene-2-norbornanone. Selective modification of the C-terminus using flavin photocatalysts in various peptides and insulin has been documented. Furthermore, for peptide substrates, use of an iridium photocatalyst (Ir[dF(CF3)ppy]2(dtbbpy)PF6, E1/2 red : 1.21 V vs SCE) alongside a polyaromatic photocatalyst (4CzIPN, E1/2 red : 1.35 V vs SCE) for C-terminal alkynylation with ethynylbenziodoxolone (EBX) reagents, and conversion of the C-terminus to N,Oacetals for electrophilic activation have been reported. Unique to Trp modification is that labeling the β-position of the Trp side chain using Ir[dF(CF3)ppy]2(dtbbpy)PF6 with Michael acceptor modification has been accomplished. In a report of Met modification, lumiflavin (E1/2 red = 1.5 V vs SCE), that is capable of accepting an electron from Met (Epa = 1.36 V vs SCE), was utilized, as reduced lumiflavin (HLF • ) facilitates proton transfer from the Met radical cation (pKa = ~3.5), acting as a base (pKa of HLF • = 8.5) and catalyzing the transfer of electrons and protons. The extension of these photocatalysts' redox cycles for peptides substrates to protein bioconjugation is based on similar mechanisms, necessitating thorough evaluation of reaction conditions to ensure orthogonality and mitigate side reactions with Michael acceptors and residues such as Cys and Lys.