ISSN:
1573-904X
Keywords:
phosphinic acid dipeptide analogue
;
nasal peptide delivery
;
transition-state analogue
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A major challenge in intranasal delivery of peptides is to overcome the enzymatic barrier that limits their absorption. Aminopeptidase inhibitors may be useful for improving systemic delivery of peptide drugs administered nasally. A phosphinic acid dipeptide analogue, a transition-state analogue aminopeptidase inhibitor in which the phosphinate moiety exists in a tetrahedral state mimicking peptides during their enzymatic hydrolysis, was synthesized and tested nasally in situ in rats. This inhibitor was found to inhibit greatly the degradation of the model peptide leucine-enkaphalin in the nasal perfusate at ≤2 µM concentrations. The nasal peptidase hydrolytic activity was reversible after exposure to the inhibitor. This inhibitor has the advantage of efficacy at very low concentrations and reversibility of effects.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015845925668
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