title: Conformational properties of secondary amino acids: replacement of pipecolic acid by N-methyl-l-alanine in efrapeptin C.
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 [MeAla(1,3) ]efrapeptin C and [MeAla(1,3,11) ]efrapeptin C inhibit ATP hydrolysis by the A3 B3 complex of A1 A0 -ATP synthase from Methanosarcina mazei Gö1.
authors.affiliation: Fakultät für Chemie, Universität Bielefeld, D-33501 Bielefeld.
authors.forename: Anita
authors.initials: A
authors.lastname: Dutt Konar
authors.forename: Elemér
authors.initials: E
authors.lastname: Vass
authors.forename: Miklós
authors.initials: M
authors.lastname: Hollósi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Majer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Grüber
authors.forename: Katrin
authors.initials: K
authors.lastname: Frese
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
mesh_terms: D000409:Alanine / Q000737:chemistry*; D007098:Imino Acids / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry*; D010875:Pipecolic Acids / Q000737:chemistry*
chemical_list: D007098:Imino Acids; D054848:Peptaibols; D010455:Peptides; D010875:Pipecolic Acids; C471725:efrapeptin C; C031345:pipecolic acid; D000409:Alanine