A. Leonebay et al., N-ACYLATED ALPHA-AMINO-ACIDS AS NOVEL ORAL DELIVERY AGENTS FOR PROTEINS, Journal of medicinal chemistry, 38(21), 1995, pp. 4263-4269
A series of N-acylated alpha-amino acids were synthesized and shown to
improve the oral delivery of two protein drugs, salmon calcitonin (sC
T) and interferon-alpha. Forty-five compounds in this series were test
ed in vivo in rats and primates. A significant positive correlation wa
s found between the log P of the acylated amino acids and the decrease
in serum calcium following oral dosage of sCT in rats. Such a correla
tion was not found for interferon-alpha. These derivatized amino acids
only weakly inhibited the activity of trypsin or leucine aminopeptida
se. Histological examinations of rat intestinal tissue after oral dosi
ng of acylated amino acid/protein combinations revealed no detectable
pathology.