A goal of our research program is the development of NADH quinone oxidoreductase type1 (NQO1) enzyme-triggered delivery agents with highly controllable stimuli-responsive behavior for eventual use in tumor-directed drug delivery systems (DDS).  One direction for such triggered DDS is the use of trigger groups that self-eliminate from the head groups upon activation (triggering) by an enzyme, such as those we have reported on that use quinone propionic acid trigger groups that take advantage of the Thorpe-Ingold Effect.  In this presentation, a new group of potential triggers based on 2-hydroxymethyl-3,5,6-trimethyl-1,4-benzoquinone (HMBQMe) is investigated.  This new trigger group upon derivatization at the 2-hydroxymethyl site can undergo 1,4-elimination reactions as a result of quinone methide formation.  The synthesis of novel HMBQMe attached fluorophores are presented, and release of the attached fluorogenic group upon reduction of quinone head group is investigated using spectroscopic methods.

Tumor targeted NQO1 activated stimuli responsive delivery systems

245th National Meeting (2013)

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