A SOLUTION NMR-STUDY OF THE SELECTIVELY C-13,N-15-LABELED PEPTAIBOL CHRYSOSPERMIN-C IN METHANOL

The conformation of the 19-residue peptaibol chrysospermin C in methan ol has been investigated by NMR spectroscopy using selective N-15 and C-13 labeling of the cr-aminoisobutyric acid (Aib) residues. Complete H-1 and C-13 sequential assignments, including stereospecific assignme nts for the heavily overlapped resonances from the two CP methyl group s of the eight Aib residues, are reported for a peptaibol for the firs t time. An Aib residue followed by a Pro is an exception to previous s uggestions regarding stereospecific assignment of the two CP methyl gr oups of Aib residues. Local nuclear Overhauser effects and (3)J(HNC') and (3)J(HNC beta) scalar couplings indicate that the phi angles of th e Aib residues are restricted sterically to local conformations consis tent with right-handed helices. Despite these constraints on the eight Aib residues, the NMR data for chrysospermin C in methanol are genera lly most consistent with an ensemble of transient conformations, inclu ding backbone conformations inconsistent with helical structures. Init ial NMR measurements for chrysospermin C bound to micelles suggest str uctural and dynamic differences relative to alamethicin bound to micel les which may be related to differences in gating voltages for formati on of ion channels.