POLY(ETHYLENE GLYCOL) DERIVATIZED PRODRUGS THROUGH MIXED DISULFIDE BOND FORMATION - PRELIMINARY-REPORT ON CAPTOPRIL

Whether or not functionalized PEGs may be useful in the case of low mo lecular weight drugs has not yet been examined so far. For that purpos e captopril, a thiol containing drug, was converted into a prodrug, ca ptopril-S-S-PEG, which does not inhibit ACE activity. The inhibitory a ction of captopril-SH can be regenerated by chemical reduction (glutha tione, DTT or NaBH4) of that prodrug. Yet, as those chemical reagents themselves partially inhibit ACE activity, the inhibitory effect of th e freed captopril-SH alone was shown to be fully recovered after coulo metric reduction.