Abstract: The present disclosure features non-canonical or heavy isotope-containing amino acids, where the alpha-amino terminus and/or carboxylic acid terminus is modified with molecular cages. The molecular cage-modified amino acids are precluded from metabolic incorporation into proteins within living bacterial, plant, or mammalian cells, or from cell-free protein expression. Once uncaged, the amino acids are readily recognized by native and/or engineered tRNA synthetases, and can subsequently be incorporated into newly-synthesized proteins during protein translation.