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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
REVIEW (Open Access)

The 9-Fluorenylmethoxycarbonyl (Fmoc) Group in Chemical Peptide Synthesis – Its Past, Present, and Future

Wenyi Li A , Neil M. O’Brien-Simpson A , Mohammed Akhter Hossain B C D and John D. Wade B C D
+ Author Affiliations
- Author Affiliations

A Bio21 Institute and Melbourne Dental School, University of Melbourne, Melbourne, Vic. 3010, Australia.

B Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic. 3010, Australia.

C School of Chemistry University of Melbourne, Melbourne, Vic. 3010, Australia.

D Corresponding authors. Email:;

Wenyi Li received his doctoral degree in 2016 from The University of Melbourne under the supervision of Professors John D. Wade and Frances Separovic. His doctoral thesis on antimicrobial peptide development won the Graham Johnston Best Thesis Award from the RACI, Australia. From 2016 to 2018, he was based at the Leibniz Institute of Molecular Pharmacology, Germany, where he was partially supported as a Leibniz-DAAD postdoctoral fellow working on protein semisynthesis and chemical ligation. In 2018, he returned to The University of Melbourne to work on antibacterial polymers and peptides in the groups of Professors Neil M. O’Brien-Simpson and Greg Qiao.

Neil M. O’Brien-Simpson graduated from Edinburgh Napier University in 1992 with a B.Sc. degree with honours in science and management studies. He moved to Australia and completed a Ph.D. in peptide-polymer vaccines in 1998 at The University of Melbourne. He is currently a professor and his research interests include antimicrobial peptides/materials, nanoparticles for peptide and vaccine delivery, and bacterial outer membrane vesicles-host interactions. He has several editorial duties and is the current president of the Peptide Users Group of the Royal Australian Chemical Institute.

Mohammed Akhter Hossain received his Ph.D. degree in 2001 from the Tokyo Institute of Technology, where he worked on chemosensors based on cyclodextrin-peptide conjugates with Professor Akihiko Ueno. After that, he was a postdoctoral fellow at the Josef Fourier University in France. In 2005, he joined the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia, where his research interests involve the design and synthesis of novel insulin and relaxin peptidomimetics, and β-amyloid peptides. He is currently a Florey Principal Research Fellow and head of the Insulin Peptides Laboratory.

John D. Wade obtained his Ph.D. degree in 1979 at Monash University, Australia, on the structural basis of the diabetogenic action of growth hormones. He received a Nuffield Foundation Fellowship to Cambridge, UK, to undertake post-doctoral studies in the laboratory of Dr R. C. Sheppard at the MRC Laboratory of Molecular Biology on the development of the Fmoc-solid phase peptide synthesis methodology. In 1983, he returned to Melbourne at the invitation of the now Florey Institute of Neuroscience and Mental Health, University of Melbourne, where he heads the Laboratory of Peptide and Protein Chemistry. His interests are in solid phase peptide synthesis of large, complex, functionalized, and often multi-chain peptides. Professor Wade is an NHMRC of Australia Principal Research Fellow and a Fellow of both the Royal Australian Chemical Institute and the Royal Society of Chemistry.

Australian Journal of Chemistry 73(4) 271-276
Submitted: 3 September 2019  Accepted: 9 October 2019   Published: 22 November 2019

Journal Compilation © CSIRO 2020 Open Access CC BY-NC-ND


The chemical formation of the peptide bond has long fascinated and challenged organic chemists. It requires not only the activation of the carboxyl group of an amino acid but also the protection of the Nα-amino group. The more than a century of continuous development of ever-improved protecting group chemistry has been married to dramatic advances in the chemical synthesis of peptides that, itself, was substantially enhanced by the development of solid-phase peptide synthesis by R. B. Merrifield in the 1960s. While the latter technology has continued to undergo further refinement and improvement in both its chemistry and automation, the development of the base-labile 9-fluorenylmethoxycarbonyl (Fmoc) group and its integration into current synthesis methods is considered a major landmark in the history of the chemical synthesis of peptides. The many beneficial attributes of the Fmoc group, which have yet to be surpassed by any other Nα-protecting group, allow very rapid and highly efficient synthesis of peptides, including ones of significant size and complexity, making it an even more valuable resource for research in the post-genomic world. This review charts the development and use of this Nα-protecting group and its adaptation to address the need for more green chemical peptide synthesis processes.


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