Recombinant protein expression, coupled with in vitro enzymatic diversifications, can sometimes enable the production of modified proteins; however, this approach is usually restricted to the transfer of PTMs to native residues with limited selectivity. Other biological approaches, such as genetic code expansion technology, can enable the insertion of desired modifications at selected sites. Unfortunately, these methods are limited by the type and number of modifications that can be introduced. Alternatively, synthetic chemistry methodologies can overcome these limitations by facilitating protein editing down to the atomic level. For instance, late-stage protein modification enables effective protein diversification starting from recombinant proteins; 9 however, this method is still limited by the type of modification and protein sequence. Importantly, the use of solid-phase peptide synthesis (SPPS) and chemoselective peptide ligations can overcome these limitations, enabling the production of modified proteins at virtually any desired site. 11 These techniques were extensively applied to probe the molecular role of the PTMs of proteins. 12 Despite these advances, the production of homogeneous proteins bearing non-proteinogenic functionalities remains challenging and rare. We envision combining a structure-based design with total synthesis and late-stage transformations will enable the development of novel abiotic proteins with enhanced properties and bioactivity.