The Utility of Oligopeptidase in Brain-Targeting Delivery of an Enkephalin Analogue by Prodrug Design

In a brain-targeting prodrug approach for a metabolically stable enkephalin analogue DADLE, specific enzymes are utilized for in vivo prodrug activation. Prolyl oligopeptidase (POP) may be especially useful in this regard. In vitro metabolic stability of the putative metabolites of prodrugs having various “spacers” has shown that POP provides significantly faster release of DADLE from conjugates having dipeptidyl spacer (specifically Xaa-Pro or Xaa-Ala) than alternative peptidases utilized when single amino acids are used as spacers. In vitro half-lives measured in rat brain homogenate showed excellent correlation with CNS-mediated analgesia using the tail-flick model in rats providing, thus, an in vivo substantiation of the prodrug approach relying on POP as the peptidase to release DADLE

Breakthroughs in medicinal chemistry: New targets and mechanisms, new drugs, new hopes–2

[No abstract available][Not available

Breakthroughs in medicinal chemistry: New targets and mechanisms, new drugs, new hopes-3

[No abstract available]Funding: The APC was sponsored by MDPI

Breakthroughs in medicinal chemistry: New targets and mechanisms, new drugs, new hopes-6

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials that is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]