Review D. Macmillan et al. Scheme 1. Some established and emerging Fmoc-based routes to thioesters. Pg = protecting group. * The scissile amide bond is N-alkylated (i.e. , R = Me or Et). This influences the position of the N !S acyl shift equilibrium because the released secondary amine is more basic. Furthermore, the released secon- dary amine is less nucleophilic and so S-peptide for- mation is favored. * The R-group can also allow additional delocalization of the amide nitrogen lone pair into an adjacent p- system, removing electron density from the amide linkage, resulting in a weaker amide bond. * The R1-group has additional functionality that can in- tercept or transform the amino group that is released upon S-peptide formation, rendering the reaction irre- versible. Derek Macmillan obtained his B.Sc. from the University of Edinburgh, then pursued a Ph.D. in bio-organic chemis- try under the supervision of Professor Sabine Flitsch, also at Edinburgh. For postdoctoral studies (1999–2001) he joined the laboratory of Professor Caro- lyn Bertozzi at UC Berkeley. After re- turning to Edinburgh as research fellow he was awarded a Royal Society Univer- sity Research Fellowship in 2003 and, following a short research visit to the laboratory of Professor Frances Arnold (CalTech), relocated to the Department of Chemistry at UCL in 2005. The Macmillan group explores the application of organic chemistry to understanding biological processes, with particular emphasis on the semisynthesis of modified proteins. Several of the developed acyl transfer facilitating devi- ces include more than one of these features. Anna Adams obtained her M.Chem. from the University of Southampton, UK (2005–2009). She subsequently was selected for the Wellcome Trust funded Ph.D. program at the Institute of Struc- tural and Molecular Biology, Birkbeck College, University College London and the National Institute for Medical Re- search in London. For her doctoral degree she is working under the guid- ance of Dr. Derek Macmillan and in collaboration with Professor Surjit Kaila S. Srai, using chemical biology tools to study the peptide hormone hepcidin, in particular working on opti- mizing the selective formation of peptide thioesters for use in Native Chemical Ligation, whilst also seeking to develop biologically active analogues to hepcidin. Bhavesh Premdjee completed his M.Sci. in Medicinal Chemistry at Uni- versity College London (2006–10) and has since undertaken a Ph.D. under the supervision of Derek Macmillan. His research focuses on the synthesis of glycoproteins. 886 www.ijc.wiley-vch.de 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Isr. J. Chem. 2011, 51, 885 – 899