VIBRATIONAL SPECTROSCOPIC DETECTION OF H-BONDED BETA-TURNS AND GAMMA-TURNS IN CYCLIC-PEPTIDES AND GLYCOPEPTIDES

The conformation of N-glycoproteins and N-glycopeptides has been the s ubject of many spectroscopic studies over the past decades. However, e xcept for some preliminary data, no detailed study on the vibrational spectroscopy of glycosylated peptides has been published until recentl y. This paper reports FTIR spectroscopic properties in DMSO and TFE of the N-glycosylated cyclic peptides cyclo[Gly-Pro-Xxx(GlcNAc)-Gly-delt a-Ava] 3a and 3b in comparison with data on the non-glycosylated paren t peptides cyclo(Gly-Pro-Xxx-Gly-delta-Ava) 2a and 2b [a, Xxx = Asn; b , Xxx = Gln; delta-Ava = NH-(CH2)(4)-CO] and N-acetyl 2-acetamido-2-de oxy-beta-D-gluco pyranosylamine (GlcNAc-NHAc, 4), The assignment of am ide I band frequencies to conformation is based on ROESY experiments a nd determination of the temperature coefficients in DMSO-d(6) solution . (For the synthesis and NMR characterization of 2a and 3a see Ref, [1 9].) Cyclic peptides are expected to adopt folded (beta- and/or gamma turn) conformations which may be fixed by intramolecular H-bonding(s). A comparison of the temperature coefficients of the NH protons and am ide I band frequencies and intensities suggests that in DMSO there is no significant difference in the backbone conformation and H-bond syst em of the N-glycosylated models and their parent cyclic peptides. The common feature of the backbone conformation of models 2 and 3 is the p redominance of a 1 <-- 4 (C-10) H-bonded type II beta-turn encompassin g Pro-Xxx or Pro-Xxx(GlcNAc), respectively. The ROESY connectivities i n the Asn(GlcNAc) model (3a) have not been found to reflect intramolec ular H-bondings between the peptide and the sugar. The unique feature of the FTIR spectra in DMSO of the cyclic models is the lack or weakne ss of low-frequency (< 1640 cm(-1)) amide I component bands, In TFE th e amide I region of the FTIR spectra shows an increased number of comp onents below 1650 cm(-1) reflecting a mixture of open and H-bonded bet a- and gamma-turn conformers, Because of its destabilizing effect upon gamma-turns and other weakly H-bonded structures, DR?SO decreases the number of backbone conformers. DMSO also destroys side-chain-backbone H-bondings of type C-7, C-6 or C-8 Possible 'glyco' C-7 H-bondings in GlcNAc-NHAc (4) or in glycopeptides 3a and 3b cannot resist the effec t of DMSO either. The FTIR data in TFE of models 2-4 suggest that the acceptor amide group of strong C-7 H-bondings in peptides and glycopep tides absorbs at 1630 +/- 5 cm(-1) and that of bifurcated H-bondings b etween 1620-1600 cm(-1). (C) 1998 Elsevier Science B.V.