Peptide Structures of the Alamethicin Sequence: The C‐Terminal α/310 Helical Nonapeptide and Two Pentapeptides with Opposite 310 Helicity

Bosch, R.; Jung, Günther; Schmitt, H.; Sheldrik, George M.; Winter, Werner

doi:10.1002/anie.198404501

Cited by 55 publications

(12 citation statements)

References 17 publications

(1 reference statement)

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“…This means that the staves of the P5 barrel seem to be built up of two head-to-tail linked helices. In fact; crystal structure analysis of 15 different Aib-containing penta-to undecapeptides (including P5a, P9 and PI1) revealed extended rods of head-to-tail linked monomers in antiparallel orientation (Bosch et al, 1984). Irrespective of a-or 310-helical structure, molecules interact by van der Waals forces of their lipophilic side chains and by one or two hydrogen bridges at the head-to-tail contact.…”

Section: Unit Channel Conductancementioning

confidence: 97%

“…The other polypeptides P9, P5, P5a and TT 13-18 also possess ordered structures. Whereas P9 adopts a mixed o#3m-helix, the short-chained peptides presumably form 310-helices as found for P5a in the crystalline state (Bosch et al, 1984). Since all these sequences are entirely hydrophobic, they are expected to incorporate spontaneously into the lipid membrane.…”

Section: Weakly Voltage-dependent Conductancementioning

confidence: 98%

“…It is worth mentioning that head-to-tail aggregation was also observed with alamethicin and trichotoxin in octanol (Schwarz & Savko, 1982;Schwarz et al, 1983). Chain lengths of the various helices were estimated in Table 5 using the following distances per amino acid (Bosch, 1984): 1.5 A (a-helix) and 2.0 A (310-helix). In case of P5 two possible chain lengths are given, because it cannot be excluded that the 310-helical pentapeptide dimer might adopt the ahelical conformation of the decapeptide under the influence of the high membrane electric field.…”

Section: Unit Channel Conductancementioning

confidence: 99%

“…In case of P5 to P20 number of experiments is given in parentheses. a Length of polypeptide chains as obtained from crystallographic data (Fox & Richards, 1982;Bosch, 1984). For details see text.…”

Section: Single Channel Current Fluctuationsmentioning

confidence: 99%

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Voltage-dependent channel formation by rods of helical polypeptides

et al. 1986

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The voltage-dependence of channel formation by alamethicin and it natural analogues can be described by a dipole flip-flop gating model, based on electric field-induced transbilayer orientational movements of single molecules. These field-induced changes in orientation result from the large permanent dipole moment of alamethicin, which adopts alpha-helical conformation in hydrophobic medium. It was, therefore, supposed that the only structural requirement for voltage-dependent formation of alamethicin-type channels might be a rigid lipophilic helical segment of minimum length. In order to test this hypothesis we synthesized a family of lipophilic polypeptides--Boc-(Ala-Aib-Ala-Aib-Ala)n-OMe, n = 1-4--which adopt alpha-helical conformation for n = 2-4 and studied their interaction with planar lipid bilayers. Surprisingly, despite their large difference in chain length, all four polypeptides showed quantitatively similar behavior. At low field strength of the membrane electric field these polypeptides induce a significant, almost voltage-independent increase of the bilayer conductivity. At high field strength, however, a strongly voltage-dependent conductance increase occurs similar to that observed with alamethicin. It results from the opening of a multitude of ion translocating channels within the membrane phase. The steady-state voltage-dependent conductance depends on the 8th-9th power of polypeptide concentration and involves the transfer of 4-5 formal elementary charges. From the power dependences on polypeptide concentration and applied voltage of the time constants in voltage-jump current-relaxation experiments, it is concluded that channels could be formed from preexisting dodecamer aggregates by the simultaneous reorientation of six formal elementary charges. Channels exhibit large conductance values of several nS, which become larger towards shorter polypeptide chain length. A mean channel diameter of 19 A is estimated corresponding roughly to the lumen diameter of a barrel comprised of 10 alpha-helical staves. Similar to experiments with the N-terminal Boc-derivative of alamethicin we did not observe the burst sequence of nonintegral conductance steps typical of natural (N-terminal Ac-Aib)-alamethicin. Saturation in current/voltage curves as well as current inactivation in voltage-jump current-relaxation experiments are found. This may be understood by assuming that channels are generated as dodecamers but, while reaching the steady state, reduce their size to that of an octamer or nonamer. We conclude that the overall behavior of these synthetic polypeptides is very similar to that of alamethicin.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Unit Channel Conductancementioning

confidence: 97%

Section: Weakly Voltage-dependent Conductancementioning

confidence: 98%

Section: Unit Channel Conductancementioning

confidence: 99%

Section: Single Channel Current Fluctuationsmentioning

confidence: 99%

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Voltage-dependent channel formation by rods of helical polypeptides

et al. 1986

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“…[29][30][31] Similarly, (Aib-Pro) n analogous sequences [32][33][34][35][36][37] reported so far, which are devoid of NH groups at alternate positions, are observed to take nearly 3 10 -helical backbone dihedral angles (referred to asbend ribbon spirals). The hydrogen-bonding pattern observed in I and R was first proposed for the (AibPro) n sequence on the basis of NMR 38 and conformational energy calculations 39 containing alternate residues devoid of NH group.…”

Section: Discussionmentioning

confidence: 95%

Stabilization of unusual structures in peptides using α,β‐dehydrophenylalanine: Crystal and solution structures of Boc–Pro–ΔPhe–Val–ΔPhe–Ala–OMe and Boc–Pro–ΔPhe–Gly–ΔPhe–Ala–OMe

et al. 2006

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The structures of two dehydropentapeptides, Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe (I) and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe (II) (Boc: t-butoxycarbonyl), have been determined by nuclear magnetic resonance (NMR), circular dichroism (CD), and X-ray crystallographic studies. The peptide I assumes a S-shaped flat beta-bend structure, characterized by two partially overlapping type II beta-bends and absence of a second 1 <-- 4 (N4--H . . . O1') intramolecular hydrogen bond. This is in contrast to the generally observed 3(10)-helical conformation in peptides with DeltaPhe at alternate positions. This report describes the novel conformation assumed by peptide I and compares it with that of the conserved tip of the V3 loop of the HIV-1 envelope glycoprotein gp120 (sequence, G:P319 to F:P324, PDB code 1ACY). The tip of the V3 loop also assumes a S-shaped conformation with Arg:P322, making an intramolecular side-chain-backbone interaction with the carbonyl oxygen of Gly:P319. Interestingly, in peptide I, C(gamma)HVal(3) makes a similar side-chain-backbone C--H . . . O hydrogen bond with the carbonyl oxygen of the Boc group. The observed overall similarity indicates the possible use of the peptide as a viral antagonist or synthetic antigen. Peptide II adopts a unique turn followed by a 3(10)-helix. Both peptides I and II are classical examples of stabilization of unusual structures in oligopeptides.

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Role of two consecutive α,β-dehydrophenylalanines in peptide structure: Crystal and molecular structure of Boc-Leu-ΔPhe-ΔPhe-Ala-Phe-NHMe

et al. 1997

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An Nα‐protected model pentapeptide containing two consecutive ΔPhe residues, Boc‐Leu‐ΔPhe‐ΔPhe‐Ala‐Phe‐NHMe, has been synthesized by solution methods and fully characterized. 1H‐nmr studies provided evidence for the occurrence of a significant population of a conformer having three consecutive, intramolecularly H‐bonded β‐bends in solution. The solid state structure has been determined by x‐ray diffraction methods. The crystals grown from aqueous methanol are orthorhombic, space group P212121, a = 11.503(2), b = 16.554(2), c = 22.107(3) Å, V = 4209(1) Å,3 and Z = 4. The x‐ray data were collected on a CAD4 diffractometer using CuKa radiation (λ = 1.5418 Å). The structure was determined using direct methods and refined by full‐matrix least‐squares procedure. The R factor is 5.3%. The molecule is characterized by a right handed 310‐helical conformation (〈ϕ〉 = −68.2°, 〈ψ〉 = −26.3°), which is made up of two consecutive type III β‐bends and one type I β‐bend. In the solid state the helical molecules are aligned head‐to‐tail, thus forming long rod like structures. A comparison with other peptide structures containing consecutive ΔPhe residues is also provided. The present study confirms that the ‐ΔPhe‐ΔPhe‐sequence can be accommodated in helical structures. © 1997 John Wiley & Sons, Inc. Biopoly 42: 373–382, 1997

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Peptide Structures of the Alamethicin Sequence: The C‐Terminal α/3₁₀ Helical Nonapeptide and Two Pentapeptides with Opposite 3₁₀ Helicity

Abstract: Z 724 IE] German version: Angew. Chem. 96 (1984) 439 CAS-Registry number: 90343-29-6. [l] a) J. Ferraris, D. 0. Cowan, V. Walatka, Jr., J. H. Perlstein, J. Am. Chem. 121 131 141 151 [61 Soc. 95 (1973) 948; b) L.

Cited by 55 publications

References 17 publications

Voltage-dependent channel formation by rods of helical polypeptides

Voltage-dependent channel formation by rods of helical polypeptides

Stabilization of unusual structures in peptides using α,β‐dehydrophenylalanine: Crystal and solution structures of Boc–Pro–ΔPhe–Val–ΔPhe–Ala–OMe and Boc–Pro–ΔPhe–Gly–ΔPhe–Ala–OMe

Role of two consecutive α,β-dehydrophenylalanines in peptide structure: Crystal and molecular structure of Boc-Leu-ΔPhe-ΔPhe-Ala-Phe-NHMe

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