Native Chemical Ligation to Minimize Aspartimide Formation during Chemical Synthesis of Small LDLa Protein

J Tailhades; A Sethi; EJ Petrie; PR Gooley; RA Bathgate; JD Wade; MA Hossain

Journal article

Native Chemical Ligation to Minimize Aspartimide Formation during Chemical Synthesis of Small LDLa Protein

J Tailhades, A Sethi, EJ Petrie, PR Gooley, RA Bathgate, JD Wade, MA Hossain

Chemistry (Weinheim an der Bergstrasse, Germany) | WILEY-V C H VERLAG GMBH | Published : 2016

DOI: 10.1002/chem.201503599

Abstract

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The inhibition of the G protein-coupled receptor, relaxin family peptide receptor 1 (RXFP1), by a small LDLa protein may be a potential approach for prostate cancer treatment. However, it is a significant challenge to chemically produce the 41-residue and three-disulfide cross-bridged LDLa module which is highly prone to aspartimide formation due to the presence of several aspartic acid residues. Known palliative measures, including addition of HOBt to piperidine for N(α) -deprotection, failed to completely overcome this side reaction. For this reason, an elegant native chemical ligation approach was employed in which two segments were assemb..

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University of Melbourne Researchers

Ashish Sethi Author

Paul Gooley Author

Ross Bathgate Author

Akhter Hossain Author

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Grants

Awarded by State Government of Victoria

Funding Acknowledgements

This research was partially funded by National Health and Medical Research Council (NHMRC) of Australia Project Grants 508995 and 1023078 (J.D.W., M.A.H., R.A.D.B.) and grants 628427 and 1043750 (R.A.D.B., P.R.G.). M.A.H. was the recipient of a Florey Foundation Fellowship, R.A.D.B. is a NHMRC Senior Research Fellow (APP1042650) and J.D.W. is an NHMRC Principal Research Fellow (APP5018148). Research at The Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Program.