Proceedings book download - 5Z.com

Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Isovaline Containing Peptides: Configurational AssignmentUsing 2D-NMR SpectroscopyMarta De Zotti 1 , Elisabetta Schievano 1 , Stefano Mammi 1 ,Bernard Kaptein 2 , Quirinus B. Broxterman 2 , Sheo B. Singh 3 ,Hans Brückner 4 , and Claudio Toniolo 11 ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, Padova, 35131,Italy; 2 DSM Innovative Synthesis, BV, Geleen, 6160 MD, The Netherlands; 3 MedicinalChemistry, Merck Research Laboratories, West Point, 07065, NJ, U.S.A.; 4 Department ofFood Sciences, University of Giessen, Giessen, 35392, GermanyIntroductionThe non-coded, C α -tetrasubstituted, chiral α-amino acid isovaline (Iva) is a characteristicmarker of a class of fungal peptide antibiotics termed peptaibiotics [1]. The unequivocaldetermination of the position and configuration of the Iva residues in peptides is imperativeif their total chemical syntheses are attempted [2]. In peptaibiotics, Iva can be of L(S)- orD(R)- configuration [3].Results and DiscussionBy 2D-NMR we investigated the naturally occurring and chemically synthesized 16-merintegramides A and B, belonging to a group of bioactive, fungal peptides (peptaibiotics)that are characterized by an abundance of Aib as well as D- and L-Iva residues. Theirprimary structures are:The chemical shifts of the C α -alkyl groups in the Iva enantiomers depend on the α-carbonchirality and on the helical screw sense of the peptides, the latter determined by CD.In the full-length, right-handed helical, integramides, as well as in the partialsequences exploited for their total chemical syntheses, the γ-methyl protons of the ethylside chain of the D-Iva residues located near the C-terminus are significantly more shielded(δ 0.95 ppm) (Figure 1).Fig. 1. Side-chain region of the TOCSY spectrum of integramide A in TFE-d 2 solution.542