An aminoboronic acid derivative inhibits thymopentin metabolism by mucosal membrane aminopeptidases.
Thymopentin is a pentapeptide with immunomodulatory activity. Transmucosal delivery may offer advantages over other routes, but published data have shown relatively poor efficacy when dosed nasally. Metabolism of thymopentin by the rat nasal mucosa and the effects of an aminoboronic acid aminopeptidase inhibitor, boroleucine, were evaluated. Thymopentin concentrations in a solution perfused through the isolated nasal cavity decayed with a first-order half-life of 12 minutes. Thymopentin was metabolized primarily by aminopeptidases, based on the amount of tetrapeptide metabolite formed. In the presence of boroleucine, at an inhibitor/substrate molar concentration ratio of 0.015/1, the degradation half-life was prolonged to 37 minutes. Appearance of the tetrapeptide metabolite of aminopeptidases was delayed. Boroleucine and other aminoboronic acid peptidase inhibitors may be useful for improving thymopentin delivery.
Hussain
M A
MA
DuPont Company, Medical Products Department, Wilmington, DE 19880-0400.
Koval
C A
CA
Shenvi
A B
AB
Aungst
B J
BJ
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D001896:Boron Compounds; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D016305:Thymopentin; D013946:Thymopoietins / Q000378:metabolism*; D013951:Thymus Hormones / Q000378:metabolism*
D001896:Boron Compounds; D010446:Peptide Fragments; D013946:Thymopoietins; D013951:Thymus Hormones; C064506:boroleucine; D000626:Aminopeptidases; D007930:Leucine; D016305:Thymopentin