α-ketoamides have vicinal (adjoining) carbonyl groups, one of which is attached to a nitrogen atom and the carbon chain, and the second of which is attached to the amide carbonyl and an alkyl or aryl group. The ketone carbonyl is rendered even more electron-deficient by the presence of the amide and thus more reactive with nucleophiles than other carbonyl groups. This electron deficiency and lack of relative steric hindrance allows for addition by nucleophilic nitrogen and sulfur atoms with protonation of the carbonyl oxygen to yield hemiaminals or thiohemiketals. If protons are available, hemiaminals can eliminate water to form imines which can undergo addition of a second nucleophile if present. Dinucleophiles with sufficiently short linking groups such as an N-terminal cysteine, serine, or threonine moiety can undergo multiple addition reactions to form thiazolidine or oxazolidine rings. The presence of lone pairs on nucleophiles and the facile deprotonation of heteroatom-hydrogen bonds renders addition to ketoamides potentially reversible; cyclization makes the reaction less likely to be reversed.