Spectroscopic evidence of beta-turn in N-glycated peptidomimetics related to leucine-enkephalin.
The conformational differences caused by N-glycation of the amide bond in endogenous opioid pentapeptide leucine-enkephalin (Tyr-Gly-Gly-Phe-Leu) have been explored in solution using FTIR spectroscopy, NMR and molecular modelling. The compounds studied include protected and unprotected enkephalin analogues N-alkylated at the second (Gly2) amino acid residue with a 6-deoxy-D-galactose moiety (1-3). Comparison of the amide I component bands in the FTIR spectra, measured in trifluoroethanol (TFE), CHCl3 and DMSO, revealed significant differences in the intensity as well as shifts in component band frequencies for glycopeptides 1-3. We found that only the FTIR spectrum of the fully protected compound 1 indicated the presence of a higher population of beta-turns, while the spectra of the partially protected and unprotected glycopeptides 2 and 3 reflected the dominance of unordered or open structures, with some low population of turns. The observed NOE connectivities in CDCl3 for both isomers of the fully protected compound 1, the all-trans one and another with Tyr1-Gly2 peptide bond in cis conformation, indicate the presence of a beta-like turn conformation. Molecular dynamics simulations of the glycopeptide 1 obtained by unconstrained energy minimization of trans- and cis-1 shows that one of trans form conformations is consistent with beta-turn whereas cis isomer has revealed less-compact turn.
Vass
E
E
Department of Organic Chemistry, Eötvös University Budapest, Hungary.
Hollósi
M
M
Kveder
M
M
Kojić-Prodić
B
B
Cudić
M B
MB
Horvat
S
S
D004745:Enkephalins / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry; D007930:Leucine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D011134:Polysaccharides / Q000737:chemistry*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D004745:Enkephalins; D006020:Glycopeptides; D011134:Polysaccharides; D007930:Leucine