Studies on the design of orally active peptide analogues.
Converting peptide inhibitors of tissue kallikrein into drugs requires, among other things, that the compounds be made orally active. Measurement of the rate at which peptides diffuse across model epithelial membranes that mimic the human gut has allowed a quantitative relationship relating lipophilicity and % absorption to be developed. The absorption of simple peptides from the human gut may be predicted with this equation.
Frigo
T B
TB
Evans Department of Clinical Research, Boston University Medical Center, MA 02118.
Burton
J
J
D000284:Administration, Oral; D002460:Cell Line; D004058:Diffusion; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015195:Drug Design; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010539:Permeability
D004151:Dipeptides; D010456:Peptides, Cyclic; D007610:Kallikreins