Patrick E. Hanna, Ph.D.
Professor of Medicinal Chemistry & Pharmacology
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Publications |
Research Interests
The primary research focus in Prof Hanna's laboratory is
on the chemical and biochemical aspects of metabolic activation
of carcinogenic arylhydroxylamines and arylhydroxamic acids.
A major objective is to gain insight into the catalytic mechanisms
and active site properties of acetyltransferases which are
involved in carcinogen activation.
Acetyltransferases (transacetylases) play a central role
in the metabolic detoxification and bioactivation of a diverse
group of drugs, carcinogens, and environmentally important
chemicals. Acetylation is a major metabolic pathway for hydrazines
(-NHNH2), hydrazides (-CONHNH2), and arylamines (ArNH2).
Acetyltransferases also catalyze the conversion of carcinogenic
arylhydroxylamines (ARNHOH) and arylhydroxamic acids (ArNOHCOCH3)
to reactive metabolites that form covalent adducts with proteins
and nucleic acids. One objective is to gain insight into
differences in the substrate specificities and active site
topologies of acetyltransferase isozymes by identifying critical
peptide and amino acid residues and elucidating their contributions
to substrate binding and catalysis. A second major objective
is to identify and characterize the arylamine-protein adducts
formed as a result of acetyltransferase-catalyzed bioactivation
of carcinogens. The results of the research will provide
a basis for understanding the functions and catalytic mechanisms
of the acetyltransferases and will contribute to definitive
characterization of the chemical mechanisms through which
the bioactivated carcinogens form adducts with their macromolecular
targets. |
