LOUISIANA CANCER RESEARCH CONSORTIUM AT XAVIER
 
 
 
Neil McIntyre, Ph.D.
seporator

  Neil McIntyre, Ph.D.
Assistant Professor of Chemistry
Telephone Number: 504-520-5083
Room Number: NCF - Room 301K
Email Address: nmcintyr@xula.edu
website: http://www.xula.edu/chemistry/profiles/nmcintyre.php

Biographical Narrative

Dr. McIntyre graduated in 2001 with a Joint Advanced Major in Chemistry and Biology from St. Francis Xavier University (Antigonish, Nova Scotia). Here, his undergraduate research project focused on the synthesis and characterization of nitrogen donor adducts and polymers of trans-bis(oxalato) ruthenium(III). In graduate school, Dr. McIntyre’s research focused on several metallo-oxygenases including tyrosinase, dopamine b-monooxygenase (DbM), and peptidylglycine a-amidating monooxygenase (PAM). Steady-state kinetics, kinetic isotope effects and computational studies of PAM was the primary research of the dissertation. During the construction of the dissertation, post-doctoral research was undertaken at the University of South Florida, College of Medicine, Department of Molecular Medicine and continued following the dissertation defense. Dr. McIntyre’s post-doctoral fellowship studied the terminal enzyme in heme biosynthesis. Here, the kinetic and resonance Raman spectroscopic characterization of ferrochelatase variants was undertaken to better understand the relationship between metal ion selectivity and porphyrin orientation. In fall 2009, Dr. McIntyre left the University of South Florida to accept an assistant professorship in the Xavier University Chemistry Department.

Research Overview

Dr. McIntyre’s research focuses on the kinetic and chemical mechanisms of peptidylglycine a-amidating monooxygenase (PAM) and related enzymes. PAM is an essential copper-, oxygen-, and ascorbate-dependent protein found in the secretory granules. In vivo, PAM post-translationally modifies COOH-terminal glycine peptide hormone precursors to their bioactive form. Using a multi-tiered approach, the mechanism of this important enzyme is examined using a balance of kinetic, chemical and theoretical approaches. Specifically, techniques such as steady-state and transient state kinetics, along with kinetic isotope effects, structure-function analysis, enzyme mutagenesis and computational simulation are used to predict and isolate chemical intermediates along the reaction coordinate. Subsequent, mechanistic information allows the design of highly specific inhibitors tailored for this reaction which is hyperactive in a number of autoimmune diseases and cancer.

Publications

Chew GH, Galloway LC, McIntyre NR, Schroder LA, Richards KM, Miller SA, Wright DW, Merkler DJ. Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha-amidating monooxygenase. FEBS Lett. 2005; 579(21): 4678-84.

McIntyre NR, Lowe EW Jr, Chew GH, Owen TC, Merkler DJ. Thiorphan, tiopronin, and related analogs as substrates and inhibitors of peptidylglycine alpha-amidating monooxygenase (PAM). FEBS Lett. 2006; 580(2):521-32.

Weiss, SJ, McIntyre, NR, McLaughlin, ML, Merkler, DJ. The development of molecular clamps as drugs. Drug Discov. Today 2006; 11(17-18):819-24.

Merkler, DJ, Asser, AS, Baumgart, LE, Carballo, N, Carpenter, SE, Chew, GH, Cosner, CC, Dusi, J, Galloway, LC, Lowe, AB, Lowe, EW Jr., King III, L, Kendig, RD, Kline, PC, Malka, R, Merkler, KA, McIntyre, NR, Romero, M, Wilcox, BJ and Owen, TC. Substituted Hippurates and Hippurate Analogs as Substrates and Inhibitors of Peptidylglycine a-Hydroxylating Monooxygenase (PHM). Bioorg Med Chem. 2008; 16(23):10061-74.

McIntyre, N.R., Lowe, E.W. Jr., and Merkler, D.J. Imino-Oxy Acetic Acid Dealkylation as Evidence for an Inner-Sphere Alcohol Intermediate in the Reaction Catalyzed by Peptidylglycine a-Hydroxylating Monooxygenase (PHM). Journal of the American Chemical Society, 2009, 131(29):10308-19.
McIntyre, N.R., Lowe, E.W.Jr., Belof,J.L., Ivkovic, M., Shafer, J., Space, B. and Merkler, D.J. Evidence for Substrate Pre-organization in the Peptidylglycine a-Amidating Monooxygenase (PAM) Reaction Describing the Contribution of Ground State Structure to Hydrogen Tunneling. Submitted.

Current support

Louisiana Cancer Research Consortium (LCRC)
Center for Undergraduate Research (CUR)

 
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