Inhibition of Peptidylglycine α-Amidating Monooxygenase by Exploitation of
Factors Affecting the Stability and Ease of Formation of Glycyl Radicals


Free radical reactions of amino acids and their derivatives are associated with a wide variety of disease states, including inflammation, and Alzheimer's and cardiovascular disease. They are also involved in the biosyntheses of many of the hormones that regulate biological activity, and are therefore intimately linked to the associated physiological and pathological conditions.



Oxidized (Cu2+) Peptidylglycine α-Hydroxylating monooxygenase (PHM) with bound substrate.

PDB ID: 10PM, S.T.Prigge, et.al., Nat.Struct.Biol. 6, 976 (1999)


This has prompted us to study aspects of the fundamental free radical reactions that are involved. Through this work we have developed models to predict the susceptibility of amino acids and peptides towards free radical processes associated with physiological disorders, and radical-resistant amino acids and peptides have been designed and synthesised. We have produced enzyme inhibitors to down-regulate, and prohormones to up-regulate, the biosynthesis of peptide hormones. We are currently evaluating the potential of these compounds as pharmaceutical agents for treating human and animal disease states associated with hormone imbalances.



Key Players

Dr. Lucy Cao
(Postdoctoral Fellow, October 2012-)

Research Topic: Inhibition of peptidylglycine α-amidating monooxygenase

Ms. Karine Caron
(PhD Student, November 2010-)

Research Topic: Inhibition of peptidylglycine α-amidating monooxygenase

Mr. Jeremy Morgan
(PhD Student, October 2012-)

Research Topic:

Mr. Chen Gu
(PhD Student, October 2012-)

Research Topic: Peptide Hormone

Ms. Daisy Zhang
(PhD Student, October 2013-)

Research Topic: Peptide Hormone


Key Publications

Beckwith memorial symposium on free radical chemistry.
Easton C.J. Aust. J. Chem ., 97 (2013), 66(3), 284-285.    DOI: 10.1071/CH13085

Production and regulation of levels of amidated peptide hormones
Cao F., Easton C.J., Aust. J. Chem ., 97 (2013), 66(3), 297-307.   DOI: 10.1071/CH12546

Prohormone-substrate peptide sequence recognition by peptidylglycine α-amidating monooxygenase and its reflection in increased glycolate inhibitor potency
Morris K.M., Cao F., Onagi H., Altamore T.M., Gamble A.B., Easton C.J., Bioorg. Med. Chem. Lett.., 97 (2012), 22(23), 7015-7018.   DOI: 10.1016/j.bmcl.2012.10.004

Free Radical Reactions in the Synthesis of α-Amino Acids and Derivatives
Easton, C. J., Chem. Rev., 97 (1997), 53-82.
DOI: 10.1021/cr930048d

Design of Radical-Resistant Amino Acid Residues: A Combined Theoretical and Experimental Investigation
Croft, A. K., Easton, C. J. and Radom, L., J. Am. Chem. Soc., 125 (2003), 4119-4124.

Inhibition of peptidylglycine a-amidating monooxygenase by exploitation of factors affecting the stability and ease of formation of glycyl radicals
Barratt, B.J.W., Easton, C.J., Henry, D.J., Li, I.H.W., Radom, L., Simpson, J.S., J. Am. Chem. Soc., 126, (2004), 13306-13311.



Research Collaborators

Free radical chemistry and biotechnology

This project is part of ARC Centre of Excellence in Free Radical Chemistry and Biotechnology.

Official website: http://www.freeradical.org.au

With C H Schiesser, J A Angus, R A J O'Hair, U Wille [U Melbourne], L Radom, M J Davies [U Sydney], P J Scammels, W R Jackson [Monash U], S E Bottle [Queensland U Technology], P J Barker [BlueScope Steel], E Rizzardo [CSIRO Molecular Health and Technologies, Melbourne], B Jarrott [Howard Florey Institute, Melbourne], C H Such [Orica Australia Pty Ltd], P Rogers [Carlton and United Breweries])



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