Peptide helices with pendant cycloalkane rings. Characterization of conformations of 1-aminocyclooctane-1-carboxylic acid (Ac8c) residues in peptides.

A pentapeptide, Boc-Leu-Ac8c-Ala-Leu-Ac8c-OMe 1, an octapeptide, Boc-Leu-Ac8c-Ala-Leu-Ac8c-Ala-Leu-Ac8c-OMe 2 and a tripeptide, Boc-Aib-Ac8c-Aib-OMe 3 containing the 1-aminocyclooctane-1-carboxylic acid residue (Ac8c) were synthesized and conformationally characterized by x-ray diffraction studies in the crystal state. Peptides 1 and 2 were also studied by NMR in CDC13 solution. Peptide 1 adopts a purely 3(10)-helical conformation in crystals, stabilized by three intramolecular 1 <-- 4 hydrogen bonds. Peptide 2 in crystals is largely 3(10)-helical with distortion in the backbone at the N-terminus by the insertion of a water molecule between Ac8c (2) CO and Ala (6) NH groups. Peptide 3 forms a C10-ring structure, i.e. a type III (III') beta- turn conformation stabilized by an intramolecular 1 <-- 4 hydrogen bond. Five cyclooctane rings assume boat-chair conformations, whereas the sixth [Ac8c(8) in 2] is appreciably distorted, resembling a chiral intermediate in the pseudorotational pathway from the boat-chair to the twisted boat-chair conformation. Internal bond angles of the cyclooctane rings are appreciably distorted from the tetrahedral value, a characteristic feature of the cyclooctane ring. Peptide 1 crystallized in the space group P212121 with a = 11.900(4) A, b = 18.728(6) A, c = 20.471(3) A and Z = 4. The final R1 and wR2 values are 0.0753 and 0.2107, respectively, for 3901 observed reflections [Fo > or = 3 sigma (Fo)]. Peptide 2 crystallized in space group P21 with a = 12.961(5) A, b = 17.710(10) A, c = 15.101(7) A, beta = 108.45(4) degrees and Z = 2. The final R1 and wR2 values are 0.0906 and 0.1832, respectively, for 2743 observed reflections [Fo > or = 3sigma (Fo)]. 1H-NMR studies on both the peptides strongly suggest the persistence of 3(10)-helical conformations in solution. Peptide 3 crystallized in the space group P21/n, with a = 10.018(1) A, b = 20.725(1) A, c = 12.915(1) A and Z = 4. The final R1 and wR2 values are 0.0411 and 0.1105, respectively, for 3634 observed reflections [Fo > or = 4sigma (Fo)].     

Conformation, hydrogen bonding and aggregate formation of guanosine 5'-monophosphate and guanosine in dimethylsulfoxide.

The tetrabutylammonium salt of guanosine 5'-monophosphate (5'-GMP) dissolves in DMSO-d6 forming aggregated species which exhibit some properties of reverse micelles. 1H NOESY experiments show that the 5'-GMP adopts the syn conformation about the glycosidic bond. Molecular mechanics calculations reveal a stable structure with this conformation in which the phosphate group and the amino group of the base are in close enough proximity to hydrogen bond. In contrast inosine 5'-monophosphate in DMSO-d6, which has no NH2 group for hydrogen bond stabilization of the syn conformation, is shown by NMR to have the anti structure. Guanosine in DMSO-d6 behaves differently from 5'-GMP. Guanosine adopts the anti conformation and forms a symmetric dimer via hydrogen bonding between the N3 and NH2 of the bases.     

High-field NMR and circular dichroism solvent-dependent conformational studies of the bradykinin C-terminal tetrapeptide Ser-Pro-Phe-Arg

The conformational properties of the tetrapeptide Ser1-Pro2-Phe3-Arg4, the C-terminal fragment of the nonapeptide hormone bradykinin, have been studied by circular dichroism and two-dimensional NMR techniques. Measurements of coupling constants, NH temperature dependence rates and nuclear Overhauser effects (performed with rotating frame nuclear Overhauser spectroscopy, ROESY) in H2O and CD3OH/D2O (80/20, v/v) reveal different conformations in the corresponding solvent. In aqueous solution the molecule exists in a random conformation or as an average of several conformations in rapid exchange. In CD3OH/D2O, however, the conformation is well-defined. The backbone of the peptide is extended, and the side-chains of Phe3 and Arg4 exhibit unusual rigidity for a peptide of this size. Evidently, the secondary structure is stabilized by a charge interaction between the guanidino group of Arg4 and the terminal carboxyl group, since experiments at various pH's show clearly that the definition of conformation decreases strongly upon protonation of the carboxyl function. A NH3+(Ser1)-COO-(Arg4) salt bridge, as well as any form of turn stabilized by hydrogen bonds can be ruled out with certainty.     

Novel phenyl(thio)ureas bearing (thio)oxothiazoline group as potential BACE-1 inhibitors: synthesis and biological evaluation

We report the synthesis and the β-site amyloid precursor protein cleaving enzyme-1 inhibitory properties of novel phenyl(thio)ureas bearing 2-(thio)oxothiazoline derivatives. A library of analogues was prepared according to specific synthetic schemes and the inhibitory activity was monitored using a fluorescence resonance energy transfer assay. Several analogues show potent inhibitory activities ranging between 1 and 0.01 µM and the activity is related to the NH acidity of the (thio)urea motif. Our results illustrate once again the close relationship between molecular recognition, complexation of the active site in enzymatic system, and organocatalysis utilizing explicit hydrogen bonding.     

Membrane channel forming polypeptides. 270-MHz proton magnetic resonance studies of the aggregation of the 11-21 fragment of suzukacillin in organic solvents

270-MHz 1H NMR studies of the 11-21 suzukacillin fragment Boc-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-G) and its analogue Boc-Ala-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-A) have been carried out in CDCl3 and (CD3)2SO. The NH chemical shifts and their temperature coefficients have been measured as a function of peptide concentration in both solvents. It is established that replacement of Gln by Ala is without effect on backbone conformation. Both peptides adopt highly folded 310 helical conformations stabilized by seven intramolecular 4 leads to hydrogen bonds. Nonlinear temperature dependences are demonstrated for free NH groups in the Gln(1) peptide. Aggregation is mediated by intermolecular hydrogen bonds formed by solvent-exposed NH groups. A major role for the Gln side chain in peptide association is suggested by differences in the NMR behavior of the Gln(1) and Ala(1) peptides. For the Gln(1) peptide in CDCl3, the carboxamide side chain carbonyl group forms an intramolecular hydrogen bond to the peptide backbone, while the trans side chain NH shows evidence for intermolecular interactions. In (CD3)2SO, the cis carboxamide NH is involved in intermolecular hydrogen bonding. The possible role of the central Gln residue in stabilizing aggregates of peptide channel formers is discussed, and a model for hexameric association is postulated.     

Synthesis of delta(E)Phe-containing tripeptide via photoisomerization and its conformation in solution

A new synthetic route to (E)-beta-phenyl-alpha,beta-dehydroalanine (delta(E)Phe)-containing peptide was presented via photochemical isomerization of the corresponding (Z)-beta-phenyl-alpha,beta-dehydroalanine (delta(Z)Phe)-containing peptide. By applying this method to Boc-Ala-delta(Z)Phe-Val-OMe (Z-I: Boc, t-butoxycarbonyl; OMe, methoxy), Boc-Ala-delta(E)Phe-Val-OMe (E-I) was obtained. The identification of peptide E-I was evidenced by 1H-nmr, 13C-nmr, and uv absorption spectroscopy, elemental analysis, and hydrogenation. The conformation of peptide E-I in CDCl3 was investigated by 1H-nmr spectroscopy (solvent dependence of NH chemical shift and difference nuclear Overhauser effect). Interestingly, peptide E-I differed from peptide Z-I in the hydrogen-bonding mode. Namely, for peptide Z-I, only Val NH participates in intramolecular hydrogen bonding, which leads to a type II beta-turn conformation supported by hydrogen bonding between CO(Boc) and NH(Val). On the other hand, for peptide E-I, two NHs, delta(E)Phe NH and Val NH, participate in intramolecular hydrogen bonding. In both peptides, a remarkable NOE (approximately 11-13%) was observed for Ala C(alpha) H-deltaPhe NH pair. Based on the nmr data and conformational energy calculation, it should be concluded that peptide E-I takes two consecutive gamma-turn conformations supported by hydrogen bonding between CO(Boc) and NH(delta(E)Phe), and between CO(Ala) and NH(Val) as its plausible conformation.     

Calix[8]arene-mediated self-assembly of tetrapeptide H-Leu-Leu-Ile-Leu-OMe

Conformational analysis of peptide 1, H-Leu-Leu-Ile-Leu-OMe on complexing with macro cycle calix[8]arene has been carried out using (1)H-NMR and FTIR spectroscopic techniques. Stoichiometry of the complex formed in the 1:8 ratio was evidenced by a Job plot. NMR studies of the above peptide show a marked downfield shift and an increase in (3)J values for NH resonances on complexing with calix[8]arene. The characteristic NOE connectivity between N(i+1)H and C(ialpha)H confirm beta-sheet conformation in the complexed state. Both (1)H-NMR and FTIR results indicate that the alpha-amino group of Leu I is proximal to the macrocycle and is involved in hydrogen bond formation with phenolic hydrogen atom of the calix[8]arene. This suggests that calix[8]arene provides a suitable platform for peptide 1 to self-assemble in a parallel beta-sheet conformation. The nature of calix[8]arene interaction with peptide 1 has been studied using dynamic NMR studies, which concludes that a bifurcated hydrogen bonding interaction exists in the molecular interfaces of the assembly.     

Solid-state conformations of aminosuccinyl peptides: crystal structure of tert-butyloxycarbonyl-L-leucyl-L-aminosuccinyl-L-phenylalaninami de

The protected tripeptide tert-butyloxycarbonyl-L-leucyl-L-aminosuccinyl-L-phenylalaninamide crystallizes in the orthorhombic space group P2(1)2(1)2(1), with a = 6.214(3), b = 12.832(3), c = 33.094(4) A, Z = 4. The structure was solved by direct methods using MULTAN 80 and refined to an R value of 0.055 for 1458 reflections. The bond lengths and angles are in good agreement with the standard values. The peptide backbone adopts a type II' beta-bend conformation with a weak intramolecular hydrogen bond between the CO group of the leucyl residue and the C-terminal NH2 group. In agreement with previous studies, this structure confirms the high propensity of aminosuccinyl peptides to adopt a type II' beta-bend conformation. The role of this conformation in relation to the deamidation process in proteins is also discussed.     

Structural basis for stabilization of Z-DNA by cobalt hexaammine and magnesium cations

In the equilibrium between B-DNA and Z-DNA in poly(dC-dG), the [Co(NH3)6]3+ ion stabilizes the Z form 4 orders of magnitude more effectively than the Mg2+ ion. The structural basis of this difference is revealed in Z-DNA crystal structures of d(CpGpCpGpCpG) stabilized by either Na+/Mg2+ or Na+/Mg2+ plus [Co(NH3)6]3+. The crystals diffract X-rays to high resolution, and the structures were refined at 1.25 A. The [Co(NH3)6]3+ ion forms five hydrogen bonds onto the surface of Z-DNA, bonding to a guanine O6 and N7 as well as to a phosphate group in the ZII conformation. The Mg2+ ion binds through its hydration shell with up to three hydrogen bonds to guanine N7 and O6. Higher charge, specific fitting of more hydrogen bonds, and a more stable complex all contribute to the great effectiveness of [Co(NH3)6]3+ in stabilizing Z-DNA.     

In vitro inhibition effects on erythrocyte carbonic anhydrase I and II and structure-activity relationships of cumarylthiazole derivatives

Coumarin and heterocyclic compounds incorporating urea have clinical applications as antiepileptics, diuretics, and antiglaucoma agents due to their carbonic anhydrase inhibitory properties. We investigated inhibition of carbonic anhydrase I and II with a series of coumarylthiazole derivatives containing urea/thiourea groups. All the investigated compounds exhibited inhibitory activity on both hCA I and hCA II, with 1-(3-chlorophenyl)-3-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea being the strongest inhibitor. Structure–activity relationship study showed that most of urea derivatives were more inhibiting for hCA I and hCA II than thiourea derivatives. The electron-withdrawing groups at the phenyl ring increased the inhibitory activity compared to electron-donating groups.     

Structural and conformational analysis of pentostatin (2'-deoxycoformycin), a potent inhibitor of adenosine deaminase

X-ray, NMR and molecular mechanics studies on pentostatin (C11H16N4O4), a potent inhibitor of the enzyme adenosine deaminase, have been carried out to study the structure and conformation. The crystals belong to the monoclinic space group P21 with the cell dimensions of a = 4.960(1), b = 10.746(3), c = 11.279(4)A, beta = 101.18(2) degrees and Z = 2. The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.047 for 997 reflections. The trihydrodiazepine ring is nonplanar and adopts a distorted sofa conformation with C(7) deviated from the mean plane by 0.66A. The deoxyribose ring adopts a C3'-endo conformation, different from coformycin where the sugar has a C2'-endo conformation. The observed glycosidic torsion angle (chi = -119.5 degrees) is in the anti range. The conformation about the C(4')-C(5') bond is gauche+. The conformation of the molecule is compared with that of coformycin and 2-azacoformycin. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. The conformation of deoxyribose in solution is approximately 70% S and 30% N. Molecular mechanics studies were performed to obtain the energy minimized conformation, which is compared with X-ray and NMR results.     

The B----Z transition in two synthetic oligonucleotides: d(C-2-amino-ACGTG) and d(m5CGCAm5CGTGCG) studied by IR, NMR and CD spectroscopies.

The sequences CA'CGTG (where A' = 2-aminodeoxyadenosine) and m5CGCAm5CGTGCG are prepared and studied by IR, CD and 1H-NMR. Infrared spectra demonstrate the capacity of the modified hexamer and decamer to adopt a Z conformation. The influence of the NH2 substitution on the adenine or of the methylated terminal part of the decamer acting with the increase of the DNA concentration stabilizes the Z conformation at room temperature in low humidity films. Very weak proportion of Z conformation is detected in UV dilute solutions. In more concentrated NMR solutions, the Z proportion induced by high salt content is only 20-25%. The effects of the concentration and of the covalent modification of the bases are discussed.     

Influence of N-terminal residue stereochemistry on the prolyl amide geometry and the conformation of 5-tert-butylproline type VI beta-turn mimics.

The effects of N-terminal amino acid stereochemistry on prolyl amide geometry and peptide turn conformation were investigated by coupling both L- and D-amino acids to (2S, 5R)-5-tert-butylproline and L-proline to generate, respectively, N-(acetyl)dipeptide N'-methylamides 1 and 2. Prolyl amide cis- and trans-isomers were, respectively, favored for peptides 1 and 2 as observed by proton NMR spectroscopy in water, DMSO and chloroform. The influence of solvent composition on amide proton chemical shift indicated an intramolecular hydrogen bond between the N'-methylamide proton and the acetamide carbonyl for the major conformer of dipeptides (S)-1, that became less favorable in (R)-1 and 2. The coupling constant (3J(NH,alpha)) values for the cis-isomer of (R)-1 indicated a phi2 dihedral angle value characteristic of a type VIb beta-turn conformation in solution. X-ray crystallographic analysis of N-acetyl-D-leucyl-5-tert-butylproline N'-methylamide (R)-lb showed the prolyl residue in a type VIb beta-turn geometry possessing an amide cis-isomer and psi3-dihedral angle having a value of 157 degrees, which precluded an intramolecular hydrogen bond. Intermolecular hydrogen bonding between the leucyl residues of two turn structures within the unit cell positioned the N-terminal residue in a geometry where their phi2 and psi2 dihedral angle values were not characteristic of an ideal type VIb turn. The circular dichroism spectra of tert-butylprolyl peptides (S)- and (R)-1b were found not to be influenced by changes in solvent composition from water to acetonitrile. The type B spectrum exhibited by (S)-1b has been previously assigned to a type VIa beta-turn conformation [Halab L, Lubell WD. J. Org. Chem. 1999; 64: 3312-3321]. The type C spectrum exhibited by the (R)-lb has previously been associated with type II' beta-turn and alpha-helical conformations in solution and appears now to be also characteristic for a type VIb geometry.     

Synthesis and structural analysis of the active enantiomer of famoxadone, a potent inhibitor of cytochrome bc1

Famoxadone is a newly commercialized fungicide and potent Qo-site inhibitor of cytochrome bc1. The S-(-)-enantiomer of famoxadone (the active component) was synthesized by two routes and was analyzed computationally and by X-ray crystallography. The molecule displays an extended conformation with flexibility in the structure imparted by the two terminal phenyl groups. In the crystal lattice, intermolecular hydrogen bonds occur between the NH and the oxygen atoms of the heterocycle.     

The synthesis and structure of the derivatives of 2-deoxy-2-hydroxyimino-D-lyxo-hexopyranosyl-L-cysteine and -thiophenol

3,4,6-Tri-O-acetyl-2-deoxy-2-hydroxyimino-beta and -alpha-D-lyxo-hexopyranosides of thiophenol (3, 4) and the methyl ester of N-benzoyl-L-cysteine have been synthesised by condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-nitroso-alpha-D-galactopyranosyl chloride with thiophenol and the L-cysteine derivative, respectively. The conformation of the sugar residue and configuration of the anomeric centre as well as of the hydroxyimino group were established on the basis of the 1H NMR (DQF-COSY, ROESY, TOCSY) spectrometric techniques and polarimetric data. Additionally, the structure of S-[3,4,6-tri-O-acetyl-2-deoxy-2-(Z)-hydroxyimino-beta-D-lyxo -hexopyranosyl]-thiophenol (3) was supported by X-ray diffraction data.     

1H-, 13C- and 31P-NMR studies of dioctanoylphosphatidylcholine and dioctanoylthiophosphatidylcholine

Coupling constants and chemical shifts were measured for dioctanoylphosphatidylcholine and its thio analogue in a CDCl3/CD3OD solvent mixture. Replacing the bridging oxygen atom of the CH-CH2-O-P portion of the phosphatidylcholine molecule with a sulfur atom affects chemical shifts and coupling constants in the glycerol backbone portion of the molecule as well as in the choline head group region. Preferred conformations about selected bonds in the phospholipids were determined from the vicinal 1H-1H, 31P-1H and 31P-13C coupling constants. A reduction of the 31P T2* (effective spin-spin relaxation time) for the thio analogue, as well as changes in the relative chemical shifts of 13C nuclei in the acyl chains, suggest a somewhat greater degree of aggregation for the thio analogue. The quadrupolar coupling constant 1J(14N-13C) for the choline methyls of either analogue, however, indicates that aggregation of these phospholipids in the CDCl3/CD3OD solvent mixture is not significant. Differences in conformation between dioctanoylphosphatidylcholine and its thio analogue may be responsible for their differences in chemical and physical properties.     

Context-dependent conformation of diethylglycine residues in peptides.

Diethylglycine (Deg) residues incorporated into peptides can stabilize fully extended (C5) or helical conformations. The conformations of three tetrapeptides Boc-Xxx-Deg-Xxx-Deg-OMe (Xxx=Gly, GD4; Leu, LD4 and Pro, PD4) have been investigated by NMR. In the Gly and Leu peptides, NOE data suggest that the local conformations at the Deg residues are fully extended. Low temperature coefficients for the Deg(2) and Deg(4) NH groups are consistent with their inaccessibility to solvent, in a C5 conformation. NMR evidence supports a folded beta-turn conformation involving Deg(2)-Gly(3), stabilized by a 4-->1 intramolecular hydrogen bond between Pro(1) CO and Deg(4) NH in the proline containing peptide (PD4). The crystal structure of GD4 reveals a hydrated multiple turn conformation with Gly(1)-Deg(2) adopting a distorted type II/II' conformation, while the Deg(2)-Pro(3) segment adopts a type III/III' structure. A lone water molecule is inserted into the potential 4-->1 hydrogen bond of the Gly(1)-Deg(2) beta-turn.     

Conformational investigation of alpha, beta-dehydropeptides. Part III. Molecular and crystal structure of acetyl-L-prolyl-alpha, beta-dehydrovaline methylamide.

The crystal structure of Ac-Pro-delta Val-NHCH3 was examined to determine the influence of the alpha,beta-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4 degrees in needle-shaped form in orthorhombic space group P2(1)2(1)2(1) with a = 11.384(2) A, b = 13.277(2) A, c = 9.942(1) A, V = 1502.7(4) A3, Z = 4, Dm = 1.17 g.cm-3 and Dc = 1.18 g.cm-3. The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a beta-bend between the type I and the type III conformation with phi 1 = -68.3(4) degrees, psi 1 = -20.1(4) degrees, phi 2 = -73.5(4) degrees and psi 2 = -14.1(4) degrees. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i + 3)th residue stabilizes the beta-bend. An additional intermolecular N...O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single alpha,beta-dehydroamino acid residue in the (i + 2) position and forming a beta-bend reveal a type II conformation.     

Switching of turn conformation in an aspartate anion peptide fragment by NH . . . O- hydrogen bonds

Aspartic acid protease model peptides Z-Phe-Asp(COOH)-Thr-Gly-Ser-Ala-NHCy (1) and AdCO-Asp(COOH)-Val-Gly-NHBzl (3), and their aspartate anions (NEt4)[Z-Phe-Asp(COO-)-Thr-Gly-Ser-Ala-NHCy] (2) and (NEt4)[AdCO-Asp(COO-)-Val-Gly-NHBzl] (4), having an invariant primary sequence of the Asp-X(Thr,Ser)-Gly fragment, were synthesized and characterized by 1H-NMR, CD, and infrared (IR) spectroscopies. NMR structure analyses indicate that the Asp O(delta) atoms of the aspartate peptide 2 are intramolecularly hydrogen-bonded with Gly, Ser, Ala NH, and Ser OH, supporting the rigid beta-turn-like conformation in acetonitrile solution. The tripeptide in the aspartic acid 3 forms an inverse gamma-turn structure, which is converted to a beta-turn-like conformation because of the formation of the intramolecular NH . . . O- hydrogen bonds with the Asp O(delta) in 4. Such a conformational change is not detected between dipeptides AdCO-Asp(COOH)-Va-NHAd (5) and (NEt4)[AdCO-Asp(COO-)-Val-NHAd] (6). The pK(a) value of side-chain carboxylic acid (5.0) for 3 exhibits a lower shift (0.3 unit) from that of 5 in aqueous polyethyleneglycol lauryl ether micellar solution. NMR structure analyses for 3 in an aqueous micellar solution indicate that the preorganized turn structure, which readily forms the NH . . . O- hydrogen bonds, lowers the pK(a) value and that resulting hydrogen bonds stabilize the rigid conformation in the aspartate anion state. We found that the formation of the NH . . . O- hydrogen bonds involved in the hairpin turn is correlated with the protonation and deprotonation state of the Asp side chain in the conserved amino acid fragments.     

Solvent-induced beta-hairpin to helix conformational transition in a designed peptide

An octapeptide containing a central -Aib-Gly- segment capable of adopting beta-turn conformations compatible with both hairpin (beta(II') or beta(I')) and helical (beta(I)) structures has been designed. The effect of solvent on the conformation of the peptide Boc-Leu-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VIII; Boc: t-butyloxycarbonyl; OMe: methyl ester) has been investigated by NMR and CD spectroscopy. Peptide VIII adopts a well-defined beta-hairpin conformation in solvents capable of hydrogen bonding like (CD(3))(2)SO and CD(3)OH. In solvents that have a lower tendency to interact with backbone peptide groups, like CDCl(3) and CD(3)CN, helical conformations predominate. Nuclear Overhauser effects between the backbone protons and solvent shielding of NH groups involved in cross-strand hydrogen bonding, backbone chemical shifts, and vicinal coupling constants provide further support for the conformational assignments in different solvents. Truncated peptides Boc-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VII), Boc-Val-Val-Aib-Gly-Leu-Val-OMe (VI), and Boc-Val-Aib-Gly-Leu-OMe (IV) were studied in CDCl(3) and (CD(3))(2)SO by 500 MHz (1)H-NMR spectroscopy. Peptides IV and VI show no evidence for hairpin conformation in both the solvents. The three truncated peptides show a well-defined helical conformation in CDCl(3). In (CD(3))(2)SO, peptide VII adopts a beta-hairpin conformation. The results establish that peptides may be designed, which are poised to undergo a dramatic conformational transition.