α-ketoamides can react with amines (both lysine and N-terminal amines), alcohols (serine and threonine residues), and thiols (cysteine residues). In actual use, the α-ketoamides boceprevir and telaprevir (Supplementary table ) inhibit hepatitis C proteases NS3/4a by reaction with their catalytic serine residues. They were approved as anti-hepatitis C agents by the US FDA in 2011, but telaprevir was withdrawn in 2014 for adverse effects, while boceprevir was withdrawn in 2015 after being superseded by newer anti-hepatits C agents. Another example of reversible covalent inhibitor containing α-ketoamide moietyis narlaprevir, also an anti-hepatitis C agent targeting the enzyme NS3/4A serine protease. Boronic acids and boronates contain a boron atom attached to carbon; boronic acids have a boron atom substituted with two hydroxy groups, while boronates are esters of boronic acids with one or both boronic acid protons substituted with alkyl or aryl groups. Boron atoms are trivalent, and unusual for main-group atoms, the boron atoms lack an octet of electrons. Boron compounds thus tend to form complexes with compounds such as amines or alcohols which have lone pairs of electrons available for donation. The complexes are formally charged because the lone pairs from the nucleophilic atom (oxygen or nitrogen) are given to boron but are less polar than depicted by the formal Lewis structures. The presence of pendant nucleophilic groups on boronates such as aldehydes can allow for tandem condensation and complexation reactions of boronates with functional groups such as amines to form adducts that do not revert easily to starting materials and thus effectively irreversible. Boronic acids and boronates commonly react with nucleophiles such as alcohols (serine and threonine residues) and amines (lysine and N-terminal amino acids) but do not form stable complexes with thiols. Boron compounds may also form complexes with imidazole rings of histidines. Examples of FDA approved boronic acid/boronate covalent inhibitors are the proteosome inhibitors bortezomib and ixazomib (Supplementary table ), which form boronate complexes with a threonine residue of the proteosome. The antibiotic tavaborole (Supplementary table ) binds to the hydroxy groups of leucyl-tRNA to prevent protein synthesis, forming a chelated complex which is not easily displaced. Vaborbactam (Supplementary table ) inhibits beta-lactamase by forming a complex with an active-site serine, preventing bacteria from inactivating β-lactam antibiotics. Aldehydes are carbonyl compounds in which one of the substituents of the carbonyl carbon is a hydrogen atom (RHC::O). Aldehydes have only one alkyl or aryl group and no electron-donating groups, so aldehydes are among the most electron-deficient of carbonyl compounds, and the presence of only one substituent makes the carbonyl carbon unhindered. Addition of a nucleophile (an amine, alcohol, or thiol) to the carbonyl carbon is thus facile and involves transfer of a proton yielding an alcohol-containing compound (a hemiaminal, hemiacetal, or hemithioacetal). Primary amines can undergo addition to aldehydes followed by elimination of water to yield an imine, which revert to amines and aldehydes much more slowly than direct addition intermediates. Aldehydes or nucleophiles with pendant nucleophiles (such as N-terminal serine, threonine, or cysteine residues) can also undergo multiple addition and elimination reactions to form oxazolidine or thiazolidine heterocycles which undergo cleavage much more slowly.