An effect of ATP on the permeability of transport-competent plasma membrane vesicles from mouse fibroblasts.

Methods for predicting peptide chain conformation have been applied to amino acid sequences adjacant to the carbohydrate attachment sites of glycoproteins containing the $\text{N}$-glycosylamine type of protein-carbohydrate linkage. Of 31 glycosylated residues examined 30 occur in sequences favouring turn or loop structures. Twentytwo of the glycosylated asparagine residues occur in tetrapeptides predicted to have the β-turn conformation. Carbohydrate attachment is therefore associated with peptide sequences which favour the formation of β-turn or other turn or loop structures.     

Characterization of β-turns in cyclic hexapeptides in solution by fourier transform IR spectroscopy

The β-turn represents a structural element frequently encountered in globular proteins. However, in spite of various theoretical and experimental studies the ir signature bands of pure β-turns are still not established beyond doubt. Although considerable information exists now on the ir spectra of β-helical and β-sheet structures, the lack of knowledge concerning turn structures in general, and that of β-turns in particular, presents a major uncertainty in the estimation of global protein secondary structures from ir spectroscopic data. To obtain more specific information about the characteristic amide bands in β-turns, we report herein an ir spectroscopic analysis of a series of five cyclic pseudo-hexapeptides known to form β-turns from previous CD and nmr studies [A. Perczel, M. Hollósi, B. M. Foxman, and G. D. Fasman (1991) Journal of the American Chemical Society, Volume 113, pp. 9772-9784 ]. We show here that in these cyclic peptides the amide groups involved in β-turns that comprise a ten-membered hydrogen-bonded ring (and represent the first H-bond pair in a β-sheet), give rise to characteristic amide I bands in the range 1638–1646 cm^?1, with the exact position depending on the solvent and the nature of the side-chain substituents. © 1993 John Wiley & Sons, Inc.     

Monte Carlo calculations on the conformations of models for the glycopeptide linkage of glycoproteins

In order to search for probable conformations of the peptide, the amino acid side chain, and the carbohydrate linkage in glycoproteins, conformational energy surfaces of glycopeptide model compounds were studied by Monte Carlo methods using the Metropolis algorithm. The potential energies were composed of empirical energy functions which include nonbonded interactions, electrostatics, hydrogen bonding, and torsional energies specified by parameters which have been used for peptides. Calculations were performed on 1-N-acetyl-2-acetamido-beta-D-glucopyranosyl amine and the glycosylated dipeptide N-acetyl-delta-N-(2-acetamido-beta-D-glucopyranosyl)-L-asparaginyl-N'-methyl amide as models for N-glycosylated peptides and on methyl-2-acetamido-alpha-D-galactopyranoside as well as the glycosylated dipeptides N-acetyl-gamma-O-(2-acetamido-alpha-D-galactopyranosyl)-L-threonyl-N'-methyl amide and its seryl analog as models for O-glycosylated glycoproteins. The probable conformations of these compounds were analyzed by single-angle probability tables and by two-dimensional conformation density maps projected from the Markov chains which contained up to six independently varied conformational dihedral angles. The presence of high barriers to rotation required the use of search strategies which resulted in a rather low acceptance rate for new conformations in the Metropolis algorithm in order to avoid trapping of the Markov chain in local energy minima. This problem contributed to the failure of these calculations to attain complete convergence to the thermodynamic limit for the glycosylated dipeptide models in which six dihedral angles were independently varied. Analysis of the results shows that the conformational space available to the highly crowded axial glycosides of the alpha-O-GalNAc type is much more restricted than that for the N-asparaginyl glycopeptides. The most probable conformation for the O-glycosylated peptides is is a beta-turn while N-glycosylated peptides may be either in a beta-turn or an extended conformation.     

Conformational interconversions in peptide β-turns: Discrimination between enantiomeric conformations by chiral perturbation

The crystal structure of the model tripeptide Boc-Aib-Gly-Leu-OMe ( 1 ) reveals two independent molecules in the asymmetric unit that adopt “enantiomeric” type I and type I′ β-turn conformations with the Aib and Gly residues occupying the corner (i + 1 and i + 2) positions. ¹³C cross polarization and magic angle sample spinning spectra in the solid state also support the coexistence of two conformational species. ¹³C-nmr in CDCl₃ establishes the presence of a single species or rapid exchange between conformations. 400 MHz ¹H-nmr provides evidence for conformational exchange involving a major and minor species, with β-turn conformations supported by the low solvent exposure of Leu(3) NH and the observation of N_iH ↔ N_i+1H nuclear Overhauser effects. CD bands in the region 190–230 nm are positive, supporting a major population of type I′ β-turns. The isomeric peptide, Boc-Gly-Leu-Aib-OMe ( 2 ), adopts an “open” type II′ β-turn conformation in crystals. Solid state and solution nmr support population of a single conformational species. Chiral perturbation introduced outside the folded region of peptides may provide a means of modulating screw sense in achiral sequences. © 1998 John Wiley & Sons, Inc. Biopoly 45: 191–202, 1998     

Type II β-turn conformation of pivaloyl-L-prolyl-α-aminoisobutyryl-N-methylamide: Theoretical,spectroscopic, and X-ray studies

Pivaloyl-L -Pro-Aib-N-methylamide has been shown to possess one intramolecular hydrogen bond in (CD₃)₂SO solution, by ¹H-nmr methods, suggesting the existence of β-turns, with Pro-Aib as the corner residues. Theoretical conformational analysis suggests that Type II β-turn conformations are about 2 kcal mol^?1 more stable than Type III structures. A crystallographic study has established the Type II β-turn in the solid state. The molecule crystallizes in the space group P2₁ with a = 5.865 Å, b = 11.421 Å, c = 12.966 Å, β = 97.55°, and Z = 2. The structure has been refined to a final R value of 0.061. The Type II β-turn conformation is stabilized by an intramolecular 4 → 1 hydrogen bond between the methylamide NH and the pivaloyl CO group. The conformational angles are ?_Pro = ?57.8°, ψ_Pro = 139.3°, ?_Aib = 61.4°, and ψ_Aib = 25.1°. The Type II β-turn conformation for Pro-Aib in this peptide is compared with the Type III structures observed for the same segment in larger peptides.     

On the location of β-turns

β-Turns are a common feature of cyclic peptides, but judging from recent x-ray and solution studies of cyclic hexapeptides it is not always possible to predict in advance the type of turn and the position of the turns in the sequence. Two or more backbone conformations containing β-turns may be of comparable energy and in rapid solvent- and temperature-dependent equilibrium in solution. The use of differential relaxation effects produced by a nitroxyl radical to locate β-turns with only minor perturbation of such equilibria is noted. Examination of the effect of a nitroxyl on the N-H resonances of the decapeptide hormone luteinizing hormone releasing hormone supports a dominant conformation with a β-turn at Gly⁶-Leu⁷. Although this turn is probably part of the biologically active conformation, it is not obvious in the more active [D -Ala⁶] analog.     

Conformations of a model cyclic hexapeptide,CYIQNC: 1H-NMR and molecular dynamics studies

Solution conformation of the cyclic hexapeptide sequence, [cyclo-S-Cys-Tyr-Ile-Gln-Asn-Cys-S] (CYIQNC) – a disulfide-linked fragment of a neurohypophyseal peptide hormone oxytocin (OT) – has been investigated by high-field one-dimensional (1D) and two-dimensional (2D) NMR spectroscopic methods and compared with the results obtained from computer simulation studies. ¹H-NMR results based on temperature dependence of amide proton chemical shifts and nuclear Overhauser effect indicate that peptide in solution populates different conformations, characterized by two fused β-turns. The segment Ile³-Gln⁴-Asn⁵-Cys⁶ yields a preferred type-III β-turn at residues 4, 5 (HB, 3HN → 6CO), while the segment Cys⁶, Cys¹-Tyr²-Ile³ exhibits inherently weaker, flexible β-turn either of type I/II’/III/half-turn at residues 1, 2 (HB, 6HN → 3CO). The computer simulation studies using a mixed protocol of distance geometry-simulated annealing followed by constrained minimization, restrained molecular dynamics, and energy minimization showed the possibility of existence of additional conformations with the hydrogen bonds, (a) 5HN → 3CO and (b) 2HN → 6CO. These results, therefore, indicate that the additional conformations obtained from both NMR and simulation studies can also be possible to the peptide. These additional conformations might have very small population in the solution and did not show their signatures in these conditions. These findings will be helpful in designing more analogs with modifications in the cyclic moiety of OT.     

Raman study of crystalline peptides containing beta turns

The Raman spectra of crystalline H-ProLeuGlyNH₂ which has a type II β turn, crystalline S-benzylCysProLeuGlyNH₂ which has a type I β-turn, and crystalline gramicidin S which has two β turns and β-sheet structure in its conformation, were investigated. The amide I and amide III bands of the peptides with β turns were generally different from those which are diagnostic for α-helix and β-sheet conformations. The patterns of the amide I and amide III bands, when examined together, indicate that Raman spectra can provide diagnostic evidence for β-turn structure in peptides.     

Prediction of the native conformation of a polypeptide by a statistical-mechanical procedure. III. Probable and average conformations of enkephalin

The program SMAPPS (Statistical-Mechanical Algorithm for Predicting Protein Structure) was originally designed to determine the probable and average backbone (?, ψ) conformations of a polypeptide by the application of equilibrium statistical mechanics in conjunction with an adaptive importance sampling Monte Carlo procedure. In the present paper, the algorithm has been extended to include the variation of all side-chain (χ) and peptide-bond (ω) dihedral angles of a polypeptide during the Monte Carlo search of the conformational space. To test the effectiveness of the generalized algorithm, SMAPPS was used to calculate the probable and average conformations of Met-enkephalin for which all dihedral angles of the pentapeptide were allowed to vary. The total conformational energy for each randomly generated structure of Met-enkephalin was obtained by summing over the interaction energies of all pairs of nonbonded atoms of the whole molecule. The interaction energies were computed by the program ECEPP /2 (Empirical Conformational Energy Program for Peptides). Solvent effects were not included in the computation. The results of the Monte Carlo calculation of the structure of Met-enkephalin indicate that the thermodynamically preferred conformation of the pentapeptide contains a γ-turn involving the three residues Gly²-Gly³-Phe⁴. The γ-turn conformation, however, does not correspond to the structure of lowest conformational energy. Rather, the global minimum-energy conformation, recently determined by a new optimization technique developed in this laboratory, contains a type II′ β-bend that is formed by the interaction of the four residues Gly²-Gly³-Phe⁴-Met⁵. A similar minimum-energy conformation is found by the SMAPPS procedure. The thermodynamically preferred γ-turn structure has a conformational energy of 4.93 kcal/mole higher than the β-bend structure of lowest energy but, because of the inclusion of entropy in the SMAPPS procedure, it is estimated to be ～ 9 kcal/mole lower in free energy. The calculation of the average conformation of Met-enkephalin was repeated until a total of ten independent average conformations were established. As far as the phenylalanine residue of the pentapeptide is concerned, the results of the ten independent average conformations were all found to lie in the region of conformational space corresponding to the γ-turn. These results further support the conclusion that the γturn conformation is thermodynamically favored.     

Conformational Analysis of the Type II and Type III Collagen α-1 Chain C-Telopeptides by 1H NMR and Circular Dichroism Spectroscopy

Abstract

The type II and type III collagen α-1 chain C-telopeptides are a 27 mer with the sequence NAc- GPGIDMSAFAGLGPREKGPDPLQYMRA and a 22mer, NAc-GGGVASLGAGEKGPVG- YGYEYR, respectively. Their conformations have been studied in CD₃OH/H₂O (80/20) solution by means of two-dimensional proton NMR and CD spectroscopy. Based on TOCSY and NOESY experiments, all resonances were assigned and the conformational properties were analyzed in terms of vicinal NH-H_α coupling constants, sequential and medium range NOEs and amide proton temperature coefficients.

The conformation of the type II C-telopeptide is essentially extended. Evidence from CD spectroscopy suggests that a very minor proportion of the peptide might be helical (ca. 8%), but the NMR data show no evidence for a non-linear structure. The observation of reduced amide proton temperature dependence coefficients in certain sections of the molecule can, in view of the absence of any other supporting evidence, only be interpreted in terms of local shielding from solvent for sterical reasons (large hydrophobic side-chains).

The conformation of the type III C-telopeptide is mostly extended except for a β-turn ranging from Gly⁸ to Glu¹¹, which is stabilized by a hydrogen-bond between NH of Glu¹¹ and the carbonyl group of Gly⁸. The low temperature coefficient of NH(Glu¹¹) and, in particular, the observation of a medium range NOE between H_α (A⁹) and NH(E¹¹) corroborate the existence of a β-turn in this region. Although spectral overlap prevents a precise conclusion with regard to the type of β-turn present, there is some evidence that it might be type II.     

Conformational energy calculations of enzyme-substrate complexes of lysozyme. I. Energy minimization of monosaccharide and oligosaccharide inhibitors and substrates of lysozyme

Conformational energy calculations were performed on monosaccharide and oligosaccharide inhibitors and substrates of lysozyme to examine the preferred conformations of these molecules. A grid-search method was used to locate all of the low-energy conformational regions for N-acetyl-β-D -glycosamine (NAG), and energy minimization was then carried out in each of these regions. Three stable positions for the N-acetyl group have ben located, in two of which the plane of the amide unit is normal to the mean plane of the pyranosyl ring. Nine local energy minima were located for the —CH₂OH group. The positions of the two vicinal cis —OH groups are determined predominantly by interactions with either the —CH₂OH or the N-acetyl group. The most stable conformations of β-N-acetylmuramic acid (NAM) were determined from the study of the low-energy conformations of NAG. In the two stable orientations for the D -lactic acid side chain, the O—C—C′ plane (C′ being the carbon atom of the terminal carboxyl group) was found to be normal to the mean plane of the pyranosyl ring. The low-energy positions for the COOH group of NAM are determined mainly by interactions with neighboring groups. The conformational preferences of the α-anomers of NAG and NAM were also explored. The calculated conformation of the N-acetyl group for α-NAG was quite close to that determined by X-ray analysis. Two of the three lowest energy conformations of α-NAM are similar to the corresponding conformations of the β-anomer. A third low-energy structure, which has a hydrogen bond from the NH of the N-acetyl group to the C?O of the lactic acid group, corresponds very closely to the X-ray structure of this molecule. The preferred conformations of the disaccharides NAG–NAG, NAM–NAG and NAG–NAM were also investigated. Two preferred orientations of the reducing pyranosyl ring relative to the nonreducing ring were found for all of these disaccharides, both of which are close to the extended conformation. In one of these conformations, a hydrogen bond can form between the OH group attached to C₃ of the reducing sugar and the ring oxygen of the preceding residue. Each conformation can be stabilized further by a hydrogen bond between the CH₂OH (donor) of residue i + 1 and the C?O of residue i (acceptor). The interactions that determine conformations for all oligosaccharides containing both NAG and NAM are shown to be exclusively intraresidue and nearest neighbor interactions, so that it is possible to predict all stable conformations of oligosaccharides containing NAG and NAM in any sequence.     

Solid-state conformations of α-Aminoisobutyryl-L-prolyl sequences: Crystal structure of Boc-Aib-L-Pro-OBzl

The protected dipeptide Boc-Aib-Pro-OBzl, C₂₁H₃₀N₂O₅, crystallizes in the orthorhombic space group P2₁2₁2₁, with a = 12.820, b = 10.529, c = 16.548Å, and Z = 4. The crystal structure has been solved by direct methods and refined to an R value of 0.074 for 1352 reflections. The Boc-Aib-Pro-OBzl molecule has been shown to adopt an unfolded conformation in the solid state with ?_Aib = 50.5°, Ψ_Aib = 45.3°, ?_Pro = ?64.6°, and Ψ_Pro = 148.1°. The result is in marked contrast with the reported crystal structure of Cbz-Aib-Pro-NHMe, which adopts an intramolecularly hydrogen-bonded β-turn conformation. Comparison with 13 reported conformations of Aib-Pro sequences in the crystalline state revealed that the Aib-Pro sequence adopts an unfolded conformation if the residue that immediately follows the dipeptide sequence possesses no hydrogen available for hydrogen bonding, while a β-turn conformation is preferred if the Pro residue is followed by an NH group. Correlation between pyrrolidine ring puckering of the Pro residue and main-chain conformation in Aib-Pro sequences is discussed.     

Vibrational analysis of peptides,polypeptides, and proteins. V. Normal vibrations of β-turns

The normal modes have been calculated for β-turns of types I, II, III, I′, II′, and III′. The complete set of frequencies is given for the first three structures; only the amide I, II, and III modes are given for the latter three structures. Calculations have been done for structures with standard dihedral angles, as well as for structures whose dihedral angles differ from these by amounts found in protein structures. The force field was that refined in our previous work on polypeptides. Transition dipole coupling was included, and is crucial to predicting frequency splittings in the amide I and amide II modes. The results show that in the amide I region, β-turn frequencies can overlap with those of the α-helix and β-sheet structures, and therefore caution must be exercised in the interpretation of protein bands in this region. The amide III modes of β-turns are predicted at significantly higher frequencies than those of α-helix and β-sheet structures, and this region therefore provides the best possibility of identifying β-turn structures. Amide V frequencies of β-turns may also be distinctive for such structures.     

β-Turn structure and intramolecular interaction of tetrapeptides containing Asp and Lys

Nmr and CD studies of terminally protected tetrapeptides were carried out in aqueous and DMSO solutions to investigate the formation and stabilization of the β-turn structure. Boc-Gly-Lys-Asp-Gly-OMe and Boc-Asp-Lys-Asp-Gly-OMe appear to have a tendency to adopt a β-turn structure in aqueous solution from the CD spectra and temperature-dependence studies of the amide proton chemical shifts. The side-chain conformation of the Asp residue depends greatly on its ionization state but was not affected by the deprotonation of the neighboring Lys side chain. There is evidence for an intramolecular interaction between the Asp and Lys side chains of Boc-Gly-Lys-Asp-Gly-OMe. Such an interaction can contribute to the stabilization of the β-turn structure.     

β-Alanine containing cyclic peptides with turned structure: The “pseudo type II β-turn.” VI

In the present paper we describe the synthesis, purification, single crystal x-ray analysis, and nmr solution characterization, combined with restrained molecular dynamic simulations, of the cyclic hexapeptide cyclo-(L -Pro-L -Phe-β-Ala)₂. The peptide was synthesized by classical solution methods and the cyclization of the free hexapeptide was accomplished in good yields in diluted methylene chloride solution using N,N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P2₁ from methanol-dichloro-methane solution. The two identical halves of the molecule adopt in the solid state two different conformations. One β-Ala-L -Pro peptide bond is trans, while the second is cis. The molecule is present in dimethylsulfoxide d₆ solutions as a mixture of conformational families. One of these corresponds to a C₂ symmetrical molecule with both β-Ala-Pro cis peptide bonds, while the second major conformation is very similar to that observed in the solid state. All Pro-Phe segments, both in the solid state and the symmetrical and unsym-metrical solution conformations, display ?,ψ angles close to that of position i + 1 and i + 2 of type II β-turns. In addition, the segments preceeded by a trans β-Ala-Pro peptide bond are characterized by a typical i ← i + 3 hydrogen bond, which is absent in the conformer containing a cis β-Ala-Pro peptide bond. The latter conformation corresponds to a new structural domain we define as the “pseudo type II β-turn.” © 1994 John Wiley & Sons, Inc.     

Introduction of a new scheme for classifying β-turns in protein structures

Protein β-turn classification remains an area of ongoing development in structural biology research. While the commonly used nomenclature defining type I, type II and type IV β-turns was introduced in the 1970s and 1980s, refinements of β-turn type definitions have been introduced as recently as 2019 by Dunbrack, Jr and co-workers who expanded the number of β-turn types to 18 (Shapovalov et al, PLOS Computat. Biol., 15, e1006844, 2019). Based on their analysis of 13 030 turns from 1074 ultrahigh resolution (≤1.2 Å) protein structures, they used a new clustering algorithm to expand the definitions used to classify protein β-turns and introduced a new nomenclature system. We recently encountered a specific problem when classifying β-turns in crystal structures of pentapeptide repeat proteins (PRPs) determined in our lab that are largely composed of β-turns that often lie close to, but just outside of, canonical β-turn regions. To address this problem, we devised a new scheme that merges the Klyne-Prelog stereochemistry nomenclature and definitions with the Ramachandran plot. The resulting Klyne-Prelog-modified Ramachandran plot scheme defines 1296 distinct potential β-turn classifications that cover all possible protein β-turn space with a nomenclature that indicates the stereochemistry of i + 1 and i + 2 backbone dihedral angles. The utility of the new classification scheme was illustrated by re-classification of the β-turns in all known protein structures in the PRP superfamily and further assessed using a database of 16 657 high-resolution protein structures (≤1.5 Å) from which 522 776 β-turns were identified and classified.     

Crystal structure and solution conformation of 1-N-acetyl-β-D-glucopyranosyl amine: A model for the glycopeptide linkage

The crystal structure of the title compound, a model for the glycosyl linkage between the asparagine side chain and N-acetyl glucosamine in glycoproteins, has been determined and compared to other model structures. The pyranose ring in the crystal is in the ⁴C₁ chair conformation and the amide functions at C₁ and at C₂ are both oriented such that the amide protons are nearly trans to their respective sugar-ring protons. Coupling constants determined from the fully assigned proton nmr spectrum in aqueous solution are consistent with the conformation in the crystal.     

Omega amino acids in peptide design: incorporation into helices

Incorporation of easily available achiral ω-amino acid residues into an oligopeptide results in substitution of amide bonds by polymethylene units of an aliphatic chain, thereby providing a convenient strategy for constructing a peptidomimetic. The central Gly-Gly segment of the helical octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-Ome(1) has been replaced by δ-amino-valeric acid (δ-Ava) residue in the newly designed peptide Boc-Leu-Aib-Val-δ-Ava-Leu-Aib-Val-OMe(2). ¹H-nmr results clearly suggest that in the apolar solvent CDCl₃, the δ-Ava residue is accommodated into a folded helical conformation, stabilized by successive hydrogen bonds involving the NH groups of Val(3), δ-Ava(4), and Leu(5). The δ-Ava residue must adopt a gauche-gauche-trans-gauche-gauche conformation along the central polymethylene unit of the aliphatic segment, a feature seen in an energy-minimized model conformation based on nmr parameters. The absence of hydrogen bonding functionalities, however, limits the elongation of the helix. In fact, in CDCl₃, the folded conformation consists of an N-terminal helix spanning residues 1–4, followed by a Type II β-turn at residues 5 and 6, whereas in strongly solvating media like (CD₃)₂SO, the unfolding of the N-terminal helix results in β-turn conformations at Leu(1)-Aib(2). The Type II β-turn at the Leu(5)-Aib(6) segment remains intact even in (CD₃)₂SO. CD comparisons of peptides 1 and 2 reveal a “nonhelical” spectrum for 2 in 2,2,2-trifluoroethanol. © 1996 John Wiley & Sons, Inc.     

Chain length effects on helix-hairpin distribution in short peptides with Aib-DAla and Aib-Aib segments

The Aib-D Ala dipeptide segment has a tendency to form both type-I'/III' and type-I/III β-turns. The occurrence of prime turns facilitates the formation of β-hairpin conformations, while type-I/III turns can nucleate helix formation. The octapeptide Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe (1) has been previously shown to form a β-hairpin in the crystalline state and in solution. The effects of sequence truncation have been examined using the model peptides Boc-Phe-Val-Aib-Xxx-Leu-Phe-NHMe (2, 6), Boc-Val-Aib-Xxx-Leu-NHMe (3, 7), and Boc-Aib-Xxx-NHMe (4, 8), where Xxx=DAla, Aib. For peptides with central Aib-Aib segments, Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe (6), Boc-Val-Aib-Aib-Leu-NHMe (7), and Boc-Aib-Aib-NHMe (8) helical conformations have been established by NMR studies in both hydrogen bonding (CD3OH) and non-hydrogen bonding (CDCl3) solvents. In contrast, the corresponding hexapeptide Boc-Phe-Val-Aib-DAla-Leu-Phe-Val-NHMe (2) favors helical conformations in CDCl3 and β-hairpin conformations in CD3 OH. The β-turn conformations (type-I'/III) stabilized by intramolecular 4→1 hydrogen bonds are observed for the peptide Boc-Aib-D Ala-NHMe (4) and Boc-Aib-Aib-NHMe (8) in crystals. The tetrapeptide Boc-Val-Aib-Aib-Leu-NHMe (7) adopts an incipient 3(10)-helical conformation stabilized by three 4→1 hydrogen bonds. The peptide Boc-Val-Aib-DAla-Leu-NHMe (3) adopts a novel α-turn conformation, stabilized by three intramolecular hydrogen bonds (two 4→1 and one 5→1). The Aib-DAla segment adopts a type-I' β-turn conformation. The observation of an NOE between Val (1) NH?HNCH3 (5) in CD3OH suggests, that the solid state conformation is maintained in methanol solutions.