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Inhibition of Peptidylglycine α-Amidating Monooxygenase by Exploitation of
Factors
Affecting the Stability and Ease of Formation of Glycyl Radicals
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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.
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Oxidized (Cu2+) Peptidylglycine α-Hydroxylating monooxygenase (PHM) with bound substrate.
PDB ID: 10PM, S.T.Prigge, et.al., Nat.Struct.Biol. 6, 976 (1999)
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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.
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Dr. Lucy Cao
(Postdoctoral Fellow, October 2012-)
Research Topic: Inhibition of peptidylglycine α-amidating monooxygenase
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Ms. Karine Caron
(PhD Student, November 2010-)
Research Topic: Inhibition of peptidylglycine α-amidating monooxygenase
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Mr. Jeremy Morgan
(PhD Student, October 2012-)
Research Topic:
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Mr. Chen Gu
(PhD Student, October 2012-)
Research Topic: Peptide Hormone
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Ms. Daisy Zhang
(PhD Student, October 2013-)
Research Topic: Peptide Hormone
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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.
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Free radical chemistry and biotechnology
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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