The zervamicins (Zrv) are a family of 16 residue peptaibol channel formers, related to the 20 residue peptaibol alamethicin (Alm), but containing a higher proportion of polar sidechains. Zrv-IIB forms multi-level channels in planar lipid (diphytanoyl phosphatidylcholine) bilayers in response to cis positive voltages. Analysis of the voltage and concentration dependence of macroscopic conductances induced by Zrv-IIB suggests that, on average, channels contain ca. 13 peptide monomers. Analysis of single channel conductance levels suggests a similar value. The pattern of successive conductance levels is consistent with a modified helix bundle model in which the higher order bundle are distorted within the plane of the bilayer towards a "torpedo" shaped cross-section. The kinetics of intra-burst switching between adjacent conductance levels are shown to be approximately an order of magnitude faster for Zrv-IIB than for Alm. The channel forming properties of the related naturally occurring peptaibols, Zrv-Leu and Zrv-IC, have also been demonstrated, as have those of the synthetic apolar analogue Zrv-Al-16. The experimental studies on channel formation are combined with the known crystallographic structures of Zrv-Al-16 and Zrv-Leu to develop a molecular model of Zrv-IIB channels.

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SynopsisThe decapeptides Boc-Aib-L-Val-Aib-Aib-(L-Val)3-Aib-L-Val-Aib-OMe and Boc-Aib-L-Leu-AibAib-(L-Leu),-Aib-L-Leu-Aib-OMe have been studied in CDC1, and (CD,),SO solutions by 270-MHz' H-nmr. In CDCl,, the presence of eight intramolecularly hydrogen-bonded N H groups has been established, consistent with a 3,,,-helical conformation, for both decapeptides. In (CD,),SO, only seven solvent-shielded NH groups are observed, supporting either an a-helical conformation or a partially unfolded 3,0-helix. Ir studies provided supporting evidence for intramolecularly hydrogen-bonded structures in CHCI,, while CD studies suggest helical conformation in both decapeptides in various solvents. CD studies also support helical folding in the C-terminal hexapeptides. The central triplet of L-amino acids appears to destabilize 3,0-helical conformations in polar solvents like (CD,),SO.

SynopsisThe conformational analysis of a protected homodipeptide of 1-aminocyclopentanecarboxylic acid (Acc5) has been carried out. 'H-nmr studies establish a p-turn conformation for Boc-Acc'. Acc'-NHMe in chloroform and dimethylsulfoxide solutions involving the methylamide NH in an intramolecular hydrogen bond. Supportive evidence for the formation of an intramolecular hydrogen bond is obtained from ir studies. X-ray diffraction studies reveal a type I11 p-turn conformation in the solid state stabilized by B 4 + 1 hydrogen bond between the Boc CO and methylamide NH groups. The +, + values for both Ace5 residues are close to those expected for an ideal 3,,,-helical conformation ( $ = f60", + = k30").

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