Conformational properties of secondary amino acids: Replacement of pipecolic acid by N-methyl-L-alanine in efrapeptin C

Anita Dutt Konar, Elemér Vass, Miklõs Hollõsi, Zsuzsanna Majer, Gerhard Grüber, Katrin Frese, Norbert Sewald

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The efrapeptins, a family of naturally occurring peptides with inhibitory activities against ATPases, contain several α,α-disubstituted α-amino acids such as α-aminoisobutyric acid (Aib) or isovaline (Iva) besides pipecolic acid (Pip), β-Ala, Leu, Gly, and a C-terminal heterocyclic residue. Secondary α-amino acids such as proline are known to stabilize discrete conformations in peptides. A similar influence is ascribed to N-alkyl α-amino acids. We synthesized two efrapeptin C analogs with replacement of Pip by N-methyl-L-alanine (MeAla) using a combination of solid- and solution-phase techniques in a fragment-condensation strategy to compare the conformational bias of both secondary amino acids. The solution conformation was investigated by vibrational circular dichroism (VCD) to probe whether the analogs adopt a 310-helical conformation. The MeAla-containing analogs [MeAla1,3]efrapeptin C and [MeAla1,3,11]efrapeptin C inhibit ATP hydrolysis by the A3B3 complex of A 1A0-ATP synthase from Methanosarcina mazei Gö1.

Original languageEnglish
Pages (from-to)942-951
Number of pages10
JournalChemistry and Biodiversity
Volume10
Issue number5
DOIs
Publication statusPublished - May 1 2013

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Keywords

  • Alanine, N-methyl-
  • Efrapeptin C
  • Helical conformation
  • Inhibitors
  • Peptaibiotics

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Molecular Medicine
  • Molecular Biology

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