In summary, we described a novel type of umpolung peptide reagents that features boronoalanine. Because BMIDA and BPai analogs are readily available in enantiomerically pure forms, incorporation of these synthons into oligopeptides and proteins that require treatments under acidic, basic, radical, and reductive conditions is now possible. Furthermore, the primary boronic esters can partake in a Pd-catalyzed cross-coupling with C(sp 2 ) electrophiles significantly expanding the chemical space of amino acids and potentially oligopeptides and proteins. In a broader sense, Ala M reagents unlock new opportunities to functionalize peptides and proteins based on umpolung of reactivity. Several important features of AlaB and its derivatives are important to highlioght. AlSMIDA and Ala BPai are compatible with standard native ligation conditions () without loss of boron or the ligands located on boron. We were able to demonstrate Scheme 2. Synthesis of AlaB ubiquitin (Phe24àAla BMIDA mutation).