Evaluation of two new coupling agents for incorporation of α,α-dialkylamino acids, such as α-methylalanine, in solid-phase peptide synthesis

Alan C. Sapia, Urszula Slomczynska, Garland R. Marshall

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The introduction of solid-phase peptide synthesis (SPPS) has greatly facilitated the preparation of peptides containing proteinaceous amino acids. Less common, sterically hindered α,α-dialkylamino acids, such as α-methylalanine (MeA, aminoisobutyric acid, Aib), have proven a synthetic challenge for incorporation by this approach, especially when present in contiguous sequences. Solution protocols, utilizing highly reactive intermediates such as oxazalones, are generally used during the preparation of peptaibol antibiotics such as alamethicin, emerimicin, etc. which contain such contiguous sequences. Two recently developed coupling strategies (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, HATU, and Fmoc-protected amino acid fluorides) allow peptides comprising contiguous sequences of α,α-dialkylamino acids to be prepared using SPPS. The present study evaluates the relative merits of these two methods on a set of difficult peptides containing oligo-MeA sequences.

Original languageEnglish
Pages (from-to)283-290
Number of pages8
JournalLetters in Peptide Science
Volume1
Issue number6
DOIs
StatePublished - May 1 1995

Keywords

  • Amino acid fluoride
  • Aminoisobutyric acid
  • Coupling reagents
  • Emerimicin
  • HATU
  • Peptaibol
  • α,α-Dialkylamino acids
  • α-Methylalanine

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