Conformation of model,alanine and proline containing tetrapeptides in water

CD spectra of model alanine and prolyl-alanine tetrapeptides were measured at different _pH values. An analysis of the spectra shows that proline in position 2 or 4 of a tetrapeptide favours folding of the peptide chain, and unfolding when it is in position 3. Changes in CD spectra evidence growing amounts of the β-turn conformation upon increasing ^pH, independent of proline position in the peptide chain.     

Conformational investigation of α,β-dehydropeptides

Conformations of three series of model peptides: homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHCH₃ (Xaa=Phe, Val, Leu. Abu. Ala) as ivell as α,β-dehydro Ac-Pro-ΔXaa-NHCH_s [ΔXaa = (Z)-ΔPhe, ΔVal. (Z)-ΔLeu, (Z)-ΔAbu] were investigated by CD spectroscopy in 2 % dichloromethanecyclohexane, trifluoroethanol. water. and occasionally in other solvents. The spectra of homochiral peptides show a significant solvent dependence. Folded structures are present in 2% dichloromethane-cyclohexane and unordered ones occur in water. The folded conformers are of the inverse γ-turn type for all the peptides but Ac-Pro-L-Phe-NHCH₃ for which the type-I β-turn is preferred. The changes in the spectra of the heterochiral peptides are limited. The compounds adopt the typc-II β–turn in 2% dichloromethanecyclohexane, represented by class B spectra, and retain this conformation in water as well as in fluorinated alcohols but not always to a full extent. The CD spectra of the unsaturated peptides in 2%, dichloromethanecyclohexane, although they cannot be assigned to any common spectral class, must be attributed to the βII-turn conformation as determined for these coinpounds by NMR and IR spectroscopy. The CD spectra of dehydropeptides exhibit a considerable solvent dependence and suggest unordered structures in water.     

Backbone—side-chain interactions in serine Synthesis,crystal structure and solution conformation of a linear model peptide N-Boc-l-Ser-l-Phe-OCH3

The peptide Boc-Ser-Phe-OCH₃ was synthesised by a solution-phase method using the usual workup procedure. The peptide was crystallized from a 70:30 (v/v) methanol-water mixture. The crystals are monoclinic, space group P2₁ with a= 5.128(2), b=17.873(2), c=11.386(2) Å, and β=98.03(3)°. The structure was determined by direct methods and refined by a structure factor least-squares procedure. The final R-value for 1499 observed reflections was 0.041. The structure contains one peptide and one solvent water molecule. The peptide adopts a β-strand-like conformation with φ₁=- 100.3(5), ψ_l= 99.9(5), φ₂= - 122.2(5), ψ^T₂= -172.5(6)°. The Ser side-chain assumes an extended conformation with χ¹₁= - 177.0(4)°. The O^γH group of serine acts as a proton donor in an intramolecular weak hydrogen bond with (Ser) O′₁; [O^γ₁;-H^γ₁?O′₁= 3.253(6) Å]. The Phe side-chain adopts a staggered conformation with χ¹₂= -70.9(6), χ²_2,1= 88.4(7)°, χ^2,2₂= -89.2(6)°. The water molecule generates a loop through two hydrogen bonds with O^γ₁ [OW?O^γ₁= 2.893(5) Å] and O′₂ [OW-O′₂= 2.962(7) Å] atoms. The unit-translated peptide molecules along the α-axis are held by hydrogen bonds: N₁-H₁?O₂ (x-1, y, z) = 2.954(4) Å and N₂-H₂?O′₁ (x+1, y, z) = 2.897(6) Å in a manner similar to those observed in parallel β-pleated sheet structures. There is an additional interaction involving O^γ₁ and the water molecule [OW?O^γ₁ (x= 1, y, z) = 2.789(4) Å]. The strong NOE peak of C_i(H)?N_i+1 (H) and a simultaneous weak NOE peak of N_i(H)?N_i+l (H) in the ROESY spectra of two-dimensional NMR in dimethyl sulfoxide indicate a β-strand-like conformation for the peptide in solution. © Munksgaard 1996.     

Synthesis and Structural Evaluations of Thiazolo[3,2-a]pyrimidine Derivatives

2-Thioxo-1,2,3,4-tetrahydropyrimidine derivatives 1 were reacted with phenacyl bromide in glacial acetic acid to obtain thiazolo[3,2-a]pyrimidine derivatives. UV-, IR-, and ¹H-NMR spectra and elementary analysis data confirm structures 3. ¹H-{¹H}-NOE techniques showed that the isolated products are H-5 isomers.     

Stabilization of β-turn conformations in enkephalins

Stereochemical constraints have been introduced into the enkephalin backbone by substituting α-aminoisobutyryl (Aib) residues at positions 2 and 3, instead of Gly. ¹H n.m.r. studies of Tyr-Aib-Gly-Phe-Met-NH₂, Tyr-Aib-Aib-Phe-Met-NH₂ and Tyr-Gly-Aib-Phe-Met-NH₂ demonstrate the occurrence of folded, intramolecularly hydrogen bonded structures in organic solvents. Similar conformations are also favoured in the corresponding t-butyloxycarbonyl protected tetrapeptides, which lack the Tyr residue. A β-turn centred at positions 2 and 3 is proposed for the Aib²-Gly³analog. In the Gly²-Aib³analog, the β-turn has Aib³-Phe⁴as the corner residues. The Aib²-Aib³analog adopts a consecutive β-turn or 3₁₀ helical conformation. High in vivo biological activity is observed for the Aib²and Aib²-Aib³analogs, while the Aib³peptide is significantly less active.     

Conformation of dehydropeptides

Six model dipeptide methyl amides containing dehydroaminobutyric acid (Δ Abu) of the type Boc-X-δ^ZAbu-NHCH₃ and Box-X-δ^EAbu-NHCH₃, X = Ala, Val, Phe (Boc =tert-butoxycarbonyl), have been synthesized and their solution conformations explored using 300 MHz ¹H NMR and IR spectroscopy. Studies based on delineation of intramolecularly hydrogen bonded NH groups in CDCl₃ and (CD₃)₂SO revealed that none of the NH groups is appreciably solvent shielded. Difference NOE (Nuclear Overhauser Effect) studies have also failed to detect the presence of any discernible turn structure in these peptides. These studies indicate that the conformational preferences of peptides containing, α, β-dehydroaminobutyric acid are different from those of Δ^ZPhe and Δ^ZLeu. It appears that steric interactions due to the β-substituent in the dehydroamino acid moiety play an important role. Unlike Δ^ZPhe and Δ^ZLeu, which have relatively large β-substituents, phenyl and isopropyl, respectively, and stabilize a β-turn, the β-methyl group of Δ^ZAbu or Δ^EAbu is readily accommodated in extended conformation. Clearly, the size of β-substituent in dehydroamino acid crucially influences the conformational preferences. Thus, it may be possible to use different dehydroamino acids to introduce variable but definite constraints in synthetic peptides.     

Conformational investigation of αβ-dehydropeptides

Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHcH₃ (Xaa = Val, Phe, Leu, Abu. Ah) as well as αβ-unsaturated Ac-Pro-ΔXaa-NHCH₃ [Δ Xaa =ΔVal, (Z)-ΔPhe, (Z)-ΔLeu, (Z)-ΔAbu] were investigated in CDCl₃ and CH₂Cl₂ by ¹H-, ¹³C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts Δδ for NH (Xaa) and NHCH₃ on going from CDCl₃ to (CD₃)₂SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and αβ-dehydropeptides (ΔXaa) on the other. Former compounds are conformationally flexible with an inverse γ-bend, a β-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and αβ-dehydropeptides are very similar, with the type-II β-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The β-turn formation propensity seems to be somewhat greater in αβ-unsaturated than in heterochiral peptides, but an estimation of β-folded conformers is risky.     

N.m.r. studies on the conformation of cyclo(-l-Trp-l-His) in solutions

N.m.r. studies on the conformations of cyclo(-l -Trp-l -His) in acidic and basic D₂O and DMSO solutions are presented here. The detailed conformational analysis of the cyclodipeptide molecule is based on ¹H chemical shifts, spin-spin coupling constants and NOE measurements. The conformational analysis consists of the following steps: 1) Calculations of the allowed {χ_n} states of the peptide molecule, (an allowed {χ_n} state is characterized by defining the two torsional angles χ₁ and χ₂ for each amino acid residue, which does not violate the excluded volume criteria). 2) Calculations of the induced chemical shifts of the His H₅ and Hβ resonances arising from the indole and imidazole ring current effects, in the various allowed {χ_n} states and the comparison of the calculated and measured chemical shifts of the above resonances. 3) The conformation of the DKP ring and the distribution of the relative populations among the three rotational isomers of each of the side chains were estimated from the measured coupling constants. Finally, the NOE measurements enabled us to determine the various pairs of protons which are spatially in close proximity to each other.     

Influence of serine in position i on conformation and dynamics of reverse turns

NMR spectroscopy has been employed for the conformational analysis of the cyclic hexapeptide cycle(-d -Pro¹-Ala²-Ser³(Bzl)-Trp⁴-Orn⁵(Z)-Tyr⁶-) with and without protecting groups on Ser³ and Orn⁵. This peptide sequence was derived from the active loop sequence of the α-amylase inhibitor Tendamistat (HOE 467). The aim was to investigate the role of serine in position i of a standard β-turn on the conformation and stabilization of this turn. Based on distance and torsion constraints from 2D NMR spectroscopic measurements in DMSO-d₆ solution, structure refinement was accomplished by restrained molecular dynamics (MD) simulations in vacuo and in DMSO. The analysis of both structures in solution reveals a considerable effect of the unprotected serine sidechain on the adjacent β-turn conformation. While in the protected peptide with Ser³(Bzl) a βII-turn is observed between Trp⁴ and Orn⁵, the deprotected compound reveals a βI-turn in this region. The βI-turn is stabilized by a backbone-sidechain hydrogen bond from Orn⁵N_αH to Ser³O_γ. Comparisons with other NMR-derived solution structures of cyclic model peptides and in some protein structures from literature reveal a general structural motif in the stabilization of βI-turns by serine in the i position through backbone-sidechain interactions. © Munksgaard 1995.     

Intramolecular H-bonds and thioamide rotational isomerism in thiopeptides

Mono- and dithionated N-acyl amino acid and dipeptide N′-methylamides were synthesized using Lawesson's reagent and 5-thioacetyl thioglycolic acid. The conformation of the thionated models was characterized by IR, ¹³C, and ¹H NMR spectroscopy, including NOE experiments. The formation of —C=S…H—N—C=X (X = O or S) intramolecular H-bonds of the type 2 → 2. 1 → 3 and 1 → 4 was evidenced by the characteristic shifts of the IR stretching frequencies of the NH group. Act-Pro-NHCH₃ (4) and Act-Prot-NHCH₃ (5) were found to be present as mixtures of rotational isomers about the CS—N bond. ¹³C chemical shifts of the γ- and β-carbons of the proline ring elucidated the conformation (Z or E) of the tertiary thioamide group. Our results suggest that the conformation of thiopeptides is determined by two factors: 1) the H-bond donating and accepting ability of the thioamide group and 2) the repulsion between the thiocarbonyl sulfur atom and the side chain groups of the neighbouring amino acid residues.     

Design of peptides with αβ-dehydro residues: Synthesis,crystal structure and molecular conformation of N-Boc-L-Ile-ΔPhe-L-Trp-OCH3

The dehydro-peptide Boc-L-Ile-ΔPhe-L-Trp-OCH₃ was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P2₁2₁2₁ with a = 10.777(2), b= 11.224(2), c= 26.627(10) Å. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [l≥ 2σ(l)].The peptide failed to adopt a folded conformation with backbone torsion angles: φ₁, = 90.8(8)°, ψ₁= -151.6(6)°, φ₂= 89.0(8)°, ψ₂= 15.9(9)°, φ₃= 165.7(7)°, ψ^T₃= -166.0(7)°. A general rule derived from earlier studies indicates that a three-peptide unit sequence with a ΔPhe at the (i+ 2) position adopts a β-turn II conformation. Because the branched β-carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the ΔPhe residue differently to generate a unique set of conformations in such peptides. The presence of β-branched residues simultaneously at both (i+ 1) and (i+ 3) positions induces unfolded conformations in tetrapeptides, but a β-branched residue substituted only at (i+ 3) positron can not prevent the formation of a folded β-turn II conformation. On the other hand, the present structure shows that a β-branched residue substituted at the (i+ 1) position prevents the formation of a β-turn II conformation. These observations indicate that a β-branched residue at the (i+ 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i+ 3) position. This may be because of the trans disposition of the planar ΔPhe side-chain with respect to the C=O group in the residue. The molecules are packed in an anti-parallel manner to generate N₂-H₂…O₂ (-x,y-1/2, -z+ 3/2) and N^ε1₃-H^ε1₃…O₁(-x,y -1/2, -z+ 3/2) hydrogen bonds.     

Synthesis and NMR conformational analysis of a β-turn mimic incorporated into gramicidin S

The solution structure of a gramicidin S (GS) analog containing a β-turn mimic[BTD^4-5, Lys^2,2′]GS has been compared to that of native GS. The linear [BTD^4-5, Lys^2,2′]GS was synthesized by solid phase methodology and the cyclized peptide was analyzed by NMR. In the peptide portion of [BTD^4-5, Lys^2,2′]GS, the intramolecular hydrogen bonding pattern, inter-residue NOEs, including a transannular Hα-Hα NOE, and J^Nα coupling constants all describe a solution structure which is equivalent to that of native GS. These data confirm that the BTD group is a competent Type II' β-turn mimic since it does not disrupt the native conformation of GS. It also supports the use of GS as a conformational model in which to test β-turn mimics.     

Cystine peptides. Spectroscopic studies on the conformations of a cyclic pentapeptide disulfide

The model cyclic pentapeptide disulfide Boc-Cys-Ala-Aib-Gly-Cys-NHMe 1, has been synthesized. ¹H n.m.r. studies in (CD₃)₂SO and CDCl₃-(CD₃)₂SO mixtures establish the solvent exposed nature of the Cys(l) and Aib NH groups, while a moderate degree of shielding is observed for the other four NH groups. Nuclear Overhauser effects between Cα₁H and N_i+1H protons provide evidence for extended or semi-extended conformations (ø ± 130° ± 30°) at the Cys(l), Ala(2), Gly(4) and Cys(5) residues. The n.m.r. results are supportive of an intramolecular antiparallel β-sheet conformation at these residues, nucleated by a γ-turn centered at Aib(3). This conformation is not stabilized by strong transannular hydrogen bonds. CD studies establish solvent dependent structural changes of the disulfide linkage in methanol-dioxane mixtures. An unusual CD pattern is observed for the peptide chromophore.     

Conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide by NMR spectroscopy

The solution conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide Tyr-d -Phe-Ser-Pro-Arg-Leu-NH₂ has been studied by NMR spectroscopy. A β-turn conformation was identified from the NOE connectivities observed for the peptide in a mixed solvent of water and DMSO, indicating that this is the biologically active conformation of the peptide. This study also suggests that the use of such an aqueous-like solvent mixture allows the observation of a preferred conformation for small linear peptides in the presence of conformational averaging.     

Comparative conformational studies on cyclic hexapeptides corresponding to message sequence His-Phe-Arg-Trp of α-Melanotropin by NMR

Solution conformation of cyclo(Gly¹-His²-Phe³-Arg⁴-Trp⁵-Gly⁶) and its d -Phe analog corresponding to the message sequence [Gly-α-MSH_5-10] of α-MSH has been studied by 1D and 2D proton magnetic resonance spectroscopy in dimethyl sulfoxide (DMSO)-d₆ solution and in a DMSO-d₆/H₂O cryoprotective mixture. The NMR data for both the analogs in solution at 300 K cannot be interpreted based on a single ordered conformation, as evidenced by the broadening of only -NH resonances as well as the temperature coefficients of the amide protons. An analysis of the nuclear Overhauser effect (NOE) cross-peaks in conjunction with temperature coefficient data indicates an equilibrium of multiple conformers with a substantial population of particular conformational states at least in the d -analog. The molecular dynamics simulations without and with NOE constraints also reveal numerous low-energy conformers with two γ-turns, a γ-turn and a β-turn, two β-turns, etc. for both the analogs. The observed NMR spectra can be rationalized by a dynamic equilibrium of conformers characterized by a γ-bend at Gly⁶, two γ-bends at Phe³ and Gly⁶ and a conformer with a single β-turn and a γ-bend for the l -Phe analog. On the other hand, a conformation with two fused β-turns around the two tetrads His²-d -Phe³-Arg⁴-Trp⁵ and Trp⁵-Gly⁶-Gly¹-His² dominates the equilibrium mixture for the d -Phe analog. For the d -Phe analog, the experimentally observed average conformation is corroborated by molecular dynamics simulations as well as by studies in cryoprotective solvent.     

Motifs and conformational analysis of amino acid residues adjoining β-turns in proteins

Using a data set of 250 non-homologous high-resolution globular proteins, a systematic analysis of the conformations that precede and succeed (positions i and i+3) the various classical β-turn types has been carried out. The collective conformation of a specific β-turn type, including the flanking positions, termed motif, has been studied. In all the four turn types, the majority of examples are preceded and succeeded by extended conformation. Some of the other observations are: (1) In a type I β-turn, Gly at position i+ 3 has a higher favorability to occur with positive ø and does not prefer the major motif βα_R-α_R-β. (2) The left-handed alpha;-helical conformation (alpha;_L) is not preferred at both the flanking positions for type I'and II β-turns, (3) The β–β motif is favourable for all the turn types and the motif β–α_L very highly favourable for type I. © Munksgaard 1996.     

Structural recognition of an ICAM-1 peptide by its receptor on the surface of T cells: conformational studies of cyclo (1, 12)-Pen-Pro-Arg-Gly-Gly-Ser-Val-Leu-Val-Thr-Gly-Cys-OH

Abstract: The purpose of this study is to elucidate the solution conformation of cyclic peptide 1 (cIBR), cyclo (1, 12)-Pen1-Pro2-Arg3-Gly4-Gly5-Ser6-Val7-Leu8-Val9-Thr10-Gly11-Cys12-OH, using NMR, circular dichroism (CD) and molecular dynamics (MD) simulation experiments. cIBR peptide ( 1 ), which is derived from the sequence of intercellular adhesion molecule-1 (ICAM-1, CD54), inhibits homotypic T-cell adhesion in vitro. The peptide hinders T-cell adhesion by inhibiting the leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18) interaction with ICAM-1. Furthermore, Molt-3 T cells bind and internalize this peptide via cell surface receptors such as LFA-1. Peptide internalization by the LFA-1 receptor is one possible mechanism of inhibition of T-cell adhesion. The recognition of the peptide by LFA-1 is due to its sequence and conformation; therefore, this study can provide a better understanding for the conformational requirement of peptide–receptor interactions. The solution structure of 1 was determined using NMR, CD and MD simulation in aqueous solution. NMR showed a major and a minor conformer due to the presence of cis/trans isomerization at the X-Pro peptide bond. Because the contribution of the minor conformer is very small, this work is focused only on the major conformer. In solution, the major conformer shows a trans-configuration at the Pen1–Pro2 peptide bond as determined by HMQC NMR. The major conformer shows possible β-turns at Pro2-Arg3-Gly4-Gly5, Gly5-Ser6-Val7-Leu8, and Val9-Thr10-Gly11-Cys12. The first β-turn is supported by the ROE connectivities between the NH of Gly4 and the NH of Gly5. The connectivities between the NH of Ser6 and the NH of Val7, followed by the interaction between the amide protons of Val7 and Leu8, support the presence of the second β-turn. Furthermore, the presence of a β-turn at Val9-Thr10-Gly11-Cys12 is supported by the NH–NH connectivities between Thr10 and Gly11 and between Gly11 and Cys12. The propensity to form a type I β-turn structure is also supported by CD spectral analysis. The cIBR peptide ( 1 ) shows structural similarity at residues Pro2 to Val7 with the same sequence in the X-ray structure of D1-domain of ICAM-1. The conformation of Pro2 to Val7 in this peptide may be important for its binding selectivity to the LFA-1 receptor.     

Stereochemistry of peptides containing 1-aminocycloheptane-1-carboxylic acid (Ac7c)

The crystal structures of four peptides incorporating l-aminocycloheptane-l-carboxylic acid (Ac₇c) are described. Boc-Aib-Ac₇c-NHMe and Boc-Pro-Ac₇c-Ala-OMe adopt β-turn conformations stabilized by an intramolecular 4 × 1 hydrogen bond, the former folding into a type-I/III β-turn and the latter into a type-II β-turn. In the dipeptide esters, Boc-Aib-Ac₇c-OMe and Boc-Pro-Ac₇c-OMe, the Ac₇c and Aib residues adopt helical conformations, while the Pro residue remains semi-extended in both the molecules of Boc-Pro-Ac₇c-OMe found in the asymmetric unit. The cycloheptane ring of Ac₇c residues adopts a twist-chair conformation in all the peptides studied. ¹H-NMR studies in CDCl₃ and (CD₃)₂SO and IR studies in CDCl₃, suggest that Boc-Aib-Ac₇c-NHMe and Boc-Pro-Ac₇c-Ala-OMe maintain the β-turn conformations in solution.     

Conformational investigation of α,β-dehydropeptides VII*. Conformation of Ac-Pro-ΔAla-NHCH3 and Ac-Pro-(E)-ΔAbu-NHCH3: comparison with (Z)-substituted α,β-dehydropeptides†

The crystal structure and solution conformation of Ac-Pro-ΔAla-NHCH₃ and the solution conformation of Ac-Pro-(E)-ΔAbu-NHCH₃ were investigated by X-ray diffraction method and NMR, FTIR and CD spectroscopies. Ac-Pro-ΔAla-NHCH, adopts an extended-coil conformation in the crystalline state, with all-trans peptide bonds and the ΔAla residue being in a C₅ form, φ₁=– 71.4(4), ψ₁=– 16.8(4), φ₂=– 178.4(3) and ψ₂= 172.4(3)°. In inert solvents the peptide also assumes the C₅ conformation, but a γ-turn on the Pro residue cannot be ruled out. In these solvents Ac-Pro-(E)- ΔAbu-NHCH₃ accommodates a βII-turn, but a minor conformer with a nearly planar disposition of the CO—NH and C=C bonds (φ₂～0°) is also present. Previous spectroscopic studies of the (Z)-substituted dehydropeptides Ac-Pro-(Z)- ΔAbu-NHCH, and Ac-Pro-ΔVal-NHCH₃ reveal that both peptides prefer a βII-turn in solution. Comparison of conformations in the family of four Ac-Pro-ΔXaa-NHCH₃ peptides let us formulate the following order of their tendency to adopt a β-turn in solution: (Z)- ΔAbu > (E)- δAbu > ΔVal; ΔAla does not. None of the folded structures formed by the four compounds is stable in strongly solvating media. © Munksgaard 1996.     

Conformations of dehydrophenylalanine containing peptides Nuclear Overhauser effect study of two acyclic tetrapeptides

Two isomeric, acyclic tetrapeptides containing a Z-dehydrophenylalanine residue (Δ^z-Phe) at position 2 or 3, Boc-Leu-Ala-Δ^z-Phe-Leu-OMe (1) and Boc-Leu-Δ^z-Phe-Ala-Leu-OMe (2), have been synthesized and their solution conformations investigated by 270MHz ¹H n.m.r. spectroscopy. In peptide 1 the Leu(4) NH group appears to be partially shielded from solvent, while in peptide 2 both Ala(3) and Leu(4) NH groups show limited solvent accessibility. Extensive difference nuclear Overhauser effect (n.O.e.) studies establish the occurrence of several diagnostic inter-residue n.O.e.s (Cα_jH ? N_i+1H and N_iH ? N_i+1H) between backbone protons. The simultaneous observation of “mutually exclusive” n.O.e.s suggests the presence of multiple solution conformations for both peptides. In peptide 1 the n.O.e. data are consistent with a dynamic equilibrium between an -Ala-Δ^z-Phe- Type II β-turn structure and a second species with Δ^z-Phe adopting a partially extended conformation with Ψ values of ± 100° to ± 150°. In peptide 2 the results are compatible with an equilibrium between a highly folded consecutive β-turn structure for the -Leu-Δ^z-Phe-Ala- segment and an almost completely extended conformation.