Stephen Chamberland, Ph.D.
Department of
Chemistry
Colorado State
University
Fort
Collins,
CO 80523
(970) 491-6668
schamber@lamar.colostate.edu
FR-900482 is a
clinically significant antitumor (anticancer) agent that structurally
resembles the mitomycins. Diverse approaches by a number of
research groups produced several total chemical syntheses of this
natural product in recent years. In addition to their structural
similarity to the mitomycins, the FR compounds are capable of forming
an electrophilic intermediate upon activation. This mitosene-like
intermediate exerts its antitumor activity by introducing interstrand
cross-links within DNA in vitro.
My research involves the
preparation of isotopically labelled compounds believed to lie early in
the biosynthetic pathway to FR-900482. In a collaborative effort
with Professor David Sherman’s laboratory at the University of Michgan,
we hope to establish these compounds as intermediates in the biogenesis
of FR-900482. In addition, identifying intermediates along the
biogenetic pathway should enable elucidation of the mechanism by which
these intermediates are produced in the organism from which FR-900482
is isolated.
Simultaneously, I am working on
two other projects involving FR-900482-based structures.
Development of a pro-mitosene compound based on FR-900482 that can be
triggered upon exposure to visible light will be difficult from a
practical standpoint, but I eagerly anticipate the challenges offered
by this project. Also, in a collaboration with Professor Raymond
Reeves of Washington State University, we hope to discover genetic
targets of FR-900482. Preparation of a biotinylated form of
FR-900482 capable of crosslinking DNA will likely foster identification
of specific genetic
targets.