title: Intramolecular acyl transfer in peptide and protein ligation and synthesis.
abstract: Intramolecular acyl transfer equilibrium in peptides and proteins has stimulated the development of new methodologies for ligation, aggregation suppression or difficult peptide synthesis. Native chemical ligation or aggregation suppression methodologies are based on an X-to-N acyl transfer of a peptide chain (X = S, O). The reverse reaction from N-to-X has led to exciting developments in solving key synthetic problems such as peptide thioester preparation using Fmoc/tBu strategy. Depending on the target peptide or protein, variations of these methods, which are also based on acyl transfer equilibriums, are now available. In this review, we provide a detailed overview of development and utility of methodologies in peptide chemistry that are based on the control of intramolecular equilibrium. To this end, we outline the scaffolds that are favorable for acyl transfer, the conditions for controlling both sides of the acyl transfer equilibrium and their applications to peptide and protein chemistry. Additional new methodologies have been developed for the synthesis of difficult peptides such as peptide alcohols or head-to-tail cyclic peptides. Promising new applications of intramolecular acyl transfer reactions are also highlighted.
authors: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, 3010, Australia.
authors: Julien
authors: J
authors: Tailhades
authors: Nitin A
authors: NA
authors: Patil
authors: Mohammed Akhter
authors: MA
authors: Hossain
authors: John D
authors: JD
authors: Wade
mesh_terms: D000215:Acylation; D000596:Amino Acids / Q000737:chemistry*; D002623:Chemistry Techniques, Analytical; D005449:Fluorenes / Q000737:chemistry*; D007700:Kinetics; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D010456:Peptides, Cyclic; D013438:Sulfhydryl Compounds
keywords: acyl transfer equilibrium; aggregation suppression; chemical ligation; head-to-tail cyclic peptides; intramolecular acyl transfer; peptide alcohols; peptide thioester synthesis; solid phase peptide synthesis