Ah. Kahns et al., PROTECTION OF THE PEPTIDE-BOND AGAINST ALPHA-CHYMOTRYPSIN BY THE PRODRUG APPROACH, Bioorganic & medicinal chemistry letters, 3(5), 1993, pp. 809-812
N-Hydroxymethylation of the N-terminal peptide bond in N-acetyl-L-phen
ylalanine amides was found to protect the C-terminal amide bond agains
t cleavage by alpha-chymotrypsin. The N-hydroxymethyl derivatives are
readily bioreversible, undergoing spontaneous hydrolysis at physiologi
cal pH, and are thus promising prodrugs to overcome the enzymatic barr
ier to absorption of various peptides.