Can one derive the conformational preference of a beta-peptide from its CD spectrum?

CD spectroscopy is often used to elucidate the secondary structure of peptides built from non-natural amino acids such as beta-amino acids. The interpretation of such CD spectra is not always unambiguous. Here, we present a case where two beta-hexapeptides, a dimethyl-beta-hexapeptide indicated as DM-BHP (A) and its nonmethylated analogue indicated as BHP (B), exhibit similar CD spectra, whereas they are expected to differ in secondary structure. The structural properties of both peptides were studied by molecular dynamics simulation, and from the resulting trajectories, the corresponding CD spectra were calculated. Starting from a fully extended conformation, BHP is observed to form a 3(14)-helix, while DM-BHP remains unfolded. However, even though these two peptides hardly share any conformations, their calculated CD spectra are alike and show the same features as the experimentally measured ones. Our results imply that a particular CD pattern can be induced by spatially different structures, which makes it difficult to derive the conformational preference of a peptide from its CD spectrum alone. To gain more insight into the relationship between the preferred conformation of a peptide and its CD spectrum, more accurate methods to calculate the CD spectrum for a given conformation are required.     

Catalysis of Hydrogen Evolution by Polylysine,Polyarginine and Polyhistidine at Mercury Electrodes

Protein catalyzed hydrogen evolution reaction at mercury‐containing electrodes controlled by constant‐current chronopotentiometric stripping (CPS) is representing a new tool useful in protein research. The resulting CPS peak H is sensitive to changes in the protein structure and its amino acid composition. Besides CPS, cyclic voltammetry appears to be useful for study of poly(amino acids) as an intermediate model system between peptides and macromolecular proteins. Here we show that similarly as arginine in polyarginine and lysine in polylysine also histidine residues in polyhistidine contribute to the catalysis of hydrogen evolution under the given conditions. Peak potentials of individual poly(amino acids) are different and depend on the type of amino acid residues.     

The N‐Terminal Nonapeptide of Cephaibols A and C: A Naturally Occurring Example of Mismatched Helical Screw‐Sense Control

The N‐terminal nonapeptide domain of the fungal nonribosomal peptide antibiotics cephaibol A and cephaibol C (AcPheAib₄LeuIvaGly‐ Aib) is reported to adopt a right‐handed helical conformation in the crystalline state. However, this conformation is at odds with the left‐handed helicity observed in solution in related synthetic oligomers capped with Ac‐L ‐PheAib₄ fragments. We report the synthesis of four diastereoisomers of the cephaibol N‐terminal nonapeptide, and show by NMR and CD spectroscopy that the peptide containing the chiral amino acids Phe and Leu in the naturally occurring relative configuration exists in solution as an interconverting mixture of helical screw‐sense conformers. In contrast, the nonapeptide containing the unnatural relative configuration at Phe and Leu adopts a single, stable helical screw‐sense, which is left handed when the N‐terminal Phe residue is L and right‐handed when the N‐terminal Phe residue is D .     

Evaluation and Comparison of a 3,5‐Dimethylphenyl Isocyanate Teicoplanin with Phenyl Isocyanate Teicoplanin Chiral Stationary Phase Using RP‐HPLC

HPLC enantiomeric separations of 8 α‐amino acids were achieved using two self‐made chiral stationary phases (CSP)–phenyl isocyanate teicoplanin (Phe‐TE) and 3,5‐dimethylphenyl isocyanate teicoplanin (DMP‐TE), using reversed phase mobile phases. The Phe‐TE or the DMP‐TE CSP was prepared from the TE using derivative agents, phenyl isocyanate or 3,5‐dimethylphenyl isocyanate, respectively. The chromatographic results were given as the retention, selectivity, resolution factor and the enantioselective free energy difference corresponding to the separation of the two enantiomers. The effect of pH, organic modifier type and amount were discussed, and the stereoselectivities for two TE‐based CSPs were compared. The chiral selectivity factor for six α‐amino acids on DMP‐TE is somewhat bigger than that on Phe‐TE CSP under reversed phase (RP) mode. Comparison of the enantiomeric separations using self‐made Phe‐TE and DMP‐TE was conducted to gain a better understanding of the chiral recognition mechanism of the macrocyclic glycopeptide CSP.     

游离芳香氨基酸和半胱氨酸对光诱导高铁肌红蛋白还原的影响

肌红蛋白(Myoglobin,Mb)中血红素辅基不仅具有储氧功能,也能吸收特定波长的光而影响蛋白功能表达。实验发现,部分游离的氨基酸对光诱导高铁肌红蛋白(metM b,Fe(III)-Mb)的还原过程及还原程度都有重要作用,因此,本文采用紫外-可见吸收光谱、圆二色谱、三维荧光光谱法,在光照体系中加入拥挤试剂来模拟细胞内拥挤环境,研究芳香氨基酸[色氨酸(Trp)、苯丙氨酸(Phe)、酪氨酸(Tyr)、半胱氨酸(Cys)]对metM b还原的影响。结果表明,含-OH或-SH的氨基酸(Tyr、Cys)能使metM b发生较好的光还原,无-OH或-SH基团的氨基酸(Trp、Phe)对metM b的光还原作用较弱,氨基酸促进metM b光还原的整个过程可能是分子间电子转移的过程。metM b在拥挤环境聚蔗糖70(Ficoll 70)中的光诱导还原程度比在稀溶液中高,拥挤试剂Ficoll70对蛋白的二级结构起保护作用,能够稳定血红素微环境。     

Theoretical Prediction of Substituent Effects on the Intrinsic Folding Properties of β‐Peptides

A systematic conformational analysis on blocked β‐amino acids as constituents of β‐peptides by ab initio MO theory reveals that the conformer pool of β‐peptide monomers is essentially determined by the conformation of simple submonomer fragments. The influence of single and multiple substitutions at the C(α) and C(β) backbone atoms on the intrinsic folding properties of the monomers was estimated both in the single‐molecule approximation and in a polar solvent continuum, applying a quantum‐chemical SCRF model. Substitution at C(β) has a higher impact on the β‐amino acid conformation than a substitution at C(α). It can be shown that the conformations of important periodic secondary structures in β‐peptides belong to the conformer pool of the monomers, even for those secondary‐structure elements where H‐bond formation appears only in longer sequences. Rules for design of special secondary‐structure types by selection of an actual substituent pattern in the β‐amino acid constituents have been derived within the monomer approach.     

Phosphoryl group differentiating α‐amino acids from β‐ and γ‐amino acids in prebiotic peptide formation

In recent years β‐amino acids have increased their importance enormously in defining secondary structures of β‐peptides. Interest in β‐amino acids raises the question: Why and how did nature choose α‐amino acids for the central role in life? In this article we present experimental results of MS and ³¹P NMR methods on the chemical behavior of N‐phosphorylated α‐alanine, β‐alanine, and γ‐amino butyric acid in different solvents. N‐Phosphoryl α‐alanine can self‐assemble to N‐phosphopeptides either in water or in organic solvents, while no assembly was observed for β‐ or γ‐amino acids. An intramolecular carboxylic–phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from α‐alanine (2a–c), with five‐membered ring, and five isomers of IMCPA derived from β‐alanine (4a–e), with six‐membered ring, were calculated with density functional theory at the B3LYP/6‐31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N‐phosphoryl α‐alanine. Both experimental and theoretical studies indicate that the structural difference among α‐, β‐, and γ‐amino acids can be recognized by formation of IMCPA after N‐phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003     

Retracted: Mass analysis by Ar‐GCIB‐dynamic SIMS for organic materials

Generally, dynamic secondary ion mass spectrometry (SIMS) has been mainly used as one of the most powerful tools for inorganic mass analysis. On the other hand, an Ar gas cluster ion beam (GCIB) has been developed and spread as a processing tool for surface flattening and also a projectile for time‐of‐flight (ToF) SIMS. In this study, we newly introduced an Ar‐GCIB as a primary ion source to a commercially available dynamic SIMS apparatus, and investigated mass spectra of amino acid films (such as Arginine and Glycine) and polymer films (Polyethylene: PE and Polypropylene: PP) as organic model samples. As a result, each characteristic fragment peak indicating the original molecular organic structure was observed in the acquired mass spectra. In addition, their own molecular ions of the amino acids were also clearly observed. Mass spectra of PE/PP blended‐polymer films acquired using Ar‐GCIB‐dynamic SIMS could be identified between pure PE and PE:PP = 1:3 mixture by applying principal component analysis (PCA).     

Array of aromatic amino acid side chains located near the chromophore of photoactive yellow protein

The role of the array of aromatic amino acid side chains located close to the chromophore binding loop of photoactive yellow protein (PYP) was studied using the alanine-substitution mutagenesis. Phe92, Tyr94, Phe96 and Tyr98 were replaced with alanine (F92A, Y94A, F96A and Y98A, respectively), then these mutants were characterized by UV-visible absorption spectra, circular dichroism (CD) spectra, thermal stability and photocycle kinetics. Absorption maxima of F92A, Y94A, F96A and Y98A were 444, 442, 439 and 447 nm, respectively, different to wild type (WT) at 446 nm. Far-UV CD spectra of mutants other than F92A were different from WT, indicating that Tyr94, Phe96 and Tyr98 maintain the native secondary structure of PYP. Mid-point temperatures of thermal denaturation of F92A, Y94A and F96A, estimated by the CD signal at 222 nm, were 5-10 degrees C lower than WT. Time constants of the photocycle estimated by flash-induced absorbance change were 0.36 s for WT and 1.4 s for Y98A, however, 100, 30 and 3000 times slower than WT for F92A, Y94A and F96A, respectively. Tyr98 is located in the loop region, whereas Phe92, Tyr94 and Phe96 are incorporated in the beta4 strand, showing that aromatic amino acid residues in the beta-sheet regulate the absorption spectrum, thermal stability and photocycle of PYP. Aromatic rings of Phe92, Tyr94 and Phe96 lie nearly perpendicular to the aromatic ring of Phe75 or chromophore. Possible weak hydrogen bonds between the aromatic ring hydrogen and pi-electrons of these residues are discussed.     

A B3LYP investigation of the conformational and environmental sensitivity of carbon�Cdeuterium frequencies of aryl-perdeuterated phenylalanine and tryptophan

Carbon?Cdeuterium labeled amino acids can serve as sensitive probes for biophysical characterization. Although multiple research groups have used infrared spectroscopy in conjunction with alkyl backbone or side-chain deuterated amino acids for the biophysical characterization of conformational and/or environmental changes, it was not entirely clear to the authors that perdeuterated aryl rings would demonstrate a similar sensitivity toward conformational or environmental changes. In an effort to evaluate the sensitivity of aryl carbon?Cdeuterium (C?CD) IR frequencies, a B3LYP investigation of the sensitivity of aryl C?CD frequencies toward conformational and environmental changes was conducted for phenylalanine (Phe) and tryptophan (Trp). To compensate for the low molar absorptivity of C?CD frequencies, perdeuterated aryl rings were investigated, which are commercially available and can be readily compared to experimental data. B3LYP results suggest that aryl-deuterated Phe and Trp will exhibit moderate sensitivities toward conformational and environmental changes with frequency shifts upward of 13 and 26?cm^?1 for Phe and Trp, respectively. B3LYP predicts that conformational sensitivity arises from dipole changes and not orbital alignment changes. In an effort to mimic what might be observed experimentally, simulated IR spectra were created and show absorption band changes with conformational and environmental changes, which indicate that IR characterization of perdeuterated aryl rings in amino acids could serve as a biophysical tool.     

Single Amino-Acid Based Self-Assembled Biomaterials with Potent Antimicrobial Activity

The design and development of soft biomaterials based on amino acid and short-peptide have gained much attention due to their potent biomedical applications. A slight alteration in the side-chain of single amino acid in a peptide or protein sequence has a huge impact on the structure and function. Phenylalanine is one of the most studied amino acids, which contains an aromatic phenyl group connected through a flexible −CH₂− unit. In this work, we have examined whether flexibility and aromatic functionality of phenylalanine (Phe) are important in gel formation of model gelator Fmoc-Phe-OH or not. To examine this hypothesis, we synthesized Fmoc-derivatives of three analogues unnatural amino acids including cyclohexylalanine, phenylglycine, and homophenylalanine; which are slightly varied from Phe. Interestingly, all these three new analogues formed hydrogels in phosphate buffer at pH 7.0 having different gelation efficacy and kinetics. This study suggests that the presence of aromatic side-chain and flexibility are not mandatory for the gelation of this model gelator. Newly synthesized unnatural amino acid derivatives have also exhibited promising antimicrobial activity towards gram-positive bacteria by inhibiting cellular oxygen consumption. We further determined the biocompatibility of these amino acid derivatives by using a hemolysis assay on human blood cells. Overall studies described the development of single amino acid-based new injectable biomaterials with improved antimicrobial activity by the slight alteration in the side-chain of amino acid.     

Prediction of glycoprotein secondary structure using ATR-FTIR

Glycoproteins are important biomolecules with a diverse array of structural and signaling functions in biology. Determination of glycoprotein secondary structure is becoming increasingly important in aiding the understanding of how these molecules function in biological environments and disease. Furthermore, glycoproteins such as mucins are being evaluated in various nano-engineering processes that require knowledge of how the underlying secondary structure might alter in different target environments. We have developed an analytical procedure for predicting the secondary structures of glycoprotein using ATR-FTIR on dry film. Using Bovine submaxillary mucin (BSM) as a glycoprotein model, we determined the additive infrared spectral pattern of acetyl amino sugars and amino acids that could contribute to the absorbance in the Amide I band of BSM through empirical data. We show through subtraction of these spectra how the absorbance pattern of the protein backbone can be determined in order to predict glycoprotein secondary structure. The analysis predicted a predominant pattern of random coil, beta sheet and beta turn secondary structure for BSM after carbohydrate and amino acid spectral subtraction in agreement with other methods. Our relatively simple approach can be applied to predict secondary structure in other glycoproteins.     

Direct Hydroxylation of Benzene to Phenol by Cytochrome P450BM3 Triggered by Amino Acid Derivatives

The selective hydroxylation of benzene to phenol, without the formation of side products resulting from overoxidation, is catalyzed by cytochrome P450BM3 with the assistance of amino acid derivatives as decoy molecules. The catalytic turnover rate and the total turnover number reached 259 min⁻¹ P450BM3⁻¹ and 40 200 P450BM3⁻¹ when N‐heptyl‐l ‐proline modified with l ‐phenylalanine (C7‐l ‐Pro‐l ‐Phe) was used as the decoy molecule. This work shows that amino acid derivatives with a totally different structure from fatty acids can be used as decoy molecules for aromatic hydroxylation by wild‐type P450BM3. This method for non‐native substrate hydroxylation by wild‐type P450BM3 has the potential to expand the utility of P450BM3 for biotransformations.     

Quantitative electrospray ionization mass spectrometric studies of ternary complexes of amino acids with Cu(2+) and phenanthroline

Electrospray ionization (ESI) mass spectra of ternary complexes of Cu(2+) and 1,10-phenanthroline with the 20 essential amino acids (AA) were investigated quantitatively. Non-basic amino acids formed singly charged complexes of the [Cu(AA - H)phen](+) type. Lysine (Lys) and arginine (Arg) formed doubly charged complexes of the [Cu(HAA - H)phen](2+) type. Detection limits were determined for the complexes of phenylalanine (Phe), glutamic acid (Glu) and Arg, which were at low micromolar or submicromolar concentrations under routine conditions. Detection limits of low nanomolar concentrations are possible for amino acids with hydrophobic side-chains (Phe, Tyr, Trp, Leu, Ile) as determined for Phe. The efficiencies for the formation by ESI of gaseous [Cu(AA - H)phen](+) ions were determined and correlated with the acid-base properties of the amino acids, ternary complex stability constants and amino acid hydrophobicities expressed as the Bull-Breese indices (DeltaF). A weak correlation was found between DeltaF and the ESI efficiencies for the formation of gaseous [Cu(AA - H)phen](+) [Cu(HAA - H]phen](2+) and [AA + H](+) ions that showed that amino acids with hydrophobic side-chains were ionized more efficiently. In the ESI of binary and ternary amino acid mixtures, the formation of gas-phase Cu-phen complexes of amino acids with hydrophobic side-chains was enhanced in the presence of complexes of amino acids with polar or basic side-chains. An interesting enhancement of the ESI formation of [Cu(Glu - H)phen](+) was observed in mixtures. The effect is explained by ion-cluster formation at the droplet interface that results in enhanced desorption of the glutamic acid complex.     

Enantioselective micellar electrokinetic chromatography of dl‐amino acids using (+)‐1‐(9‐fluorenyl)‐ethyl chloroformate derivatization and UV‐induced fluorescence detection

Chiral analysis of dl ‐amino acids was achieved by micellar electrokinetic chromatography coupled with UV‐excited fluorescence detection. The fluorescent reagent (+)‐1‐(9‐fluorenyl)ethyl chloroformate was employed as chiral amino acid derivatizing agent and sodium dodecyl sulfate served as pseudo‐stationary phase for separating the formed amino acid diastereomers. Sensitive analysis of (+)‐1‐(9‐fluorenyl)ethyl chloroformate‐amino acids was achieved applying a xenon‐mercury lamp for ultraviolet excitation, and a spectrograph and charge‐coupled device for wavelength‐resolved emission detection. Applying signal integration over a 30 nm emission wavelength interval, signal‐to‐noise ratios for derivatized amino acids were up to 23 times higher as obtained using a standard photomultiplier for detection. The background electrolyte composition (electrolyte, pH, sodium dodecyl sulfate concentration, and organic solvent) was studied in order to attain optimal chemo‐ and enantioseparation. Enantioseparation of 12 proteinogenic dl ‐amino acids was achieved with chiral resolutions between 1.2 and 7.9, and detection limits for most derivatized amino acids in the 13–60 nM range (injected concentration). Linearity (coefficients of determination > 0.985) and peak‐area and migration‐time repeatabilities (relative standard deviations lower than 2.6 and 1.9%, respectively) were satisfactory. The employed fluorescence detection system provided up to 100‐times better signal‐to‐noise ratios for (+)‐1‐(9‐fluorenyl)ethyl chloroformate‐amino acids than ultraviolet absorbance detection, showing good potential for d ‐amino acid analysis.     

Designing Point Mutants to Detect Structural Coupling in a Heterotrimeric G Protein α‐subunit by NMR Spectroscopy†

To better understand the mechanism by which the activating signal is transmitted from the receptor‐interacting regions on the G protein α‐subunit (G_α) to the guanine nucleotide‐binding pocket, we generated and characterized mutant forms of G_α with alterations in switch II (Trp‐207→Phe) and the carboxyl‐terminus (Phe‐350→Ala). Previously reported bacterial expression methods for the high‐level production of a uniformly isotope‐labeled G_tα/G_i1α chimera, ChiT, were successfully used to isolate milligram quantities of ¹⁵N‐labeled mutant protein. NMR analysis showed that while the GDP/Mg²⁺‐bound state of both mutants shared an overall conformation similar to that of the GDP/Mg²⁺‐bound state of ChiT, formation of the “transition/activated” state in the presence of aluminum fluoride (AlF₄^?) revealed distinct differences between the wild‐type and mutant G_α subunits, particularly in the response of the ¹HN, ¹⁵N cross‐peak for the Trp‐254 indole in the Trp‐207→Phe mutant and the ¹HN, ¹⁵N cross‐peak for Ala‐350 in the Phe‐350→Ala mutant. Consistent with the NMR data, the F350→Ala mutant showed an increase in intrinsic fluorescence that was similar to G_tα and ChiT upon formation of the “transition/activated” state in the presence of AlF₄^?, whereas the intrinsic fluorescence of the Trp‐207→Phe mutant decreased. These results show that the substitution of key amino acid positions in G_α can effect structural changes that may compromise receptor interactions and GDP/GTP exchange.     

Putative One‐Pot Prebiotic Polypeptides with Ribonucleolytic Activity

KIA7, a peptide with a highly restricted set of amino acids (Lys, Ile, Ala, Gly and Tyr), adopts a specifically folded structure. Some amino acids, including Lys, Ile, Ala, Gly and His, form under the same putative prebiotic conditions, whereas different conditions are needed for producing Tyr, Phe and Trp. Herein, we report the 3D structure and conformational stability of the peptide KIA7H, which is composed of only Lys, Ile, Ala, Gly and His. When the imidazole group is neutral, this 20‐mer peptide adopts a four‐helix bundle with a specifically packed hydrophobic core. Therefore, one‐pot prebiotic proteins with well‐defined structures might have arisen early in chemical evolution. The Trp variant, KIA7W, was also studied. It adopts a 3D structure similar to that of KIA7H and its previously studied Tyr and Phe variants, but is remarkably more stable. When tested for ribonucleolytic activity, KIA7H, KIA7W and even short, unstructured peptides rich in His and Lys, in combination with Mg⁺⁺, Mn⁺⁺ or Ni⁺⁺ (but not Cu⁺⁺, Zn⁺⁺ or EDTA) specifically cleave the single‐stranded region in an RNA stem–loop. This suggests that prebiotic peptide–divalent cation complexes with ribonucleolytic activity might have co‐inhabited the RNA world.     

An Investigation of Protonation Sites and Conformations of Protonated Amino Acids by IRMPD Spectroscopy

The protonation sites and structures of a series of protonated amino acids (Gly, Ala, Pro, Phe, Lys and Ser) are investigated by means of infrared multiple‐photon dissociation (IRMPD) spectroscopy and electronic‐structure calculations. The IRMPD spectra of the protonated species are recorded using the combination of a free‐electron laser (FEL) and an electrospray‐ion‐trap mass spectrometer. The structures of different possible isomers of these protonated species are optimized at the B3LYP/6‐311+G(d, p) level of theory and the IR spectra calculated using the same computational method. For every amino acid studied herein, the current results indicate that a proton is bound to the α‐amino nitrogen, except for lysine, in which the protonation site is the amino nitrogen in the side chain. According to the calculated and experimental IRMPD results, the structures of the protonated amino acids may be assigned unambiguously. For Gly, Ala, and Pro, in each of the most stable isomers the protonated amino group forms an intramolecular hydrogen bond with the adjacent carbonyl oxygen. In the case of Gly, the isomer containing a proton bound to the carbonyl oxygen is theoretically possible. However, it does not exist under the experimental conditions because it has a significantly higher energy (i.e. 26.6 kcal mol^?1) relative to the most stable isomer. For Ser and Phe, the protonated amino group forms two intramolecular hydrogen bonds with both the adjacent carbonyl oxygen and the side‐chain group in each of the most stable isomers. In protonated lysine, the protonated amino group in the side chain forms two hydrogen bonds with the α‐amino nitrogen and the carbonyl oxygen, which is a cyclic structure. Interestingly, for protonated lysine the zwitterionic structure is a local minimum energy isomer, but the experimental spectrum indicates that it does not exist under the experimental conditions. This is consistent with the fact that the zwitterionic isomer is 9.2 kcal mol^?1 higher in free energy at 298 K than the most stable isomer. The carbonyl stretching vibration in the range of 1760–1800 cm^?1 is especially sensitive to the structural change. In addition, IRMPD mechanisms for the protonated amino acids are also investigated.     

Peptide models XXXI. Conformational properties of hydrophobic residues shaping the core of proteins. An ab initio study of N‐formyl‐L‐valinamide and N‐formyl‐L‐phenylalaninamide

Employing introductory (3‐21G RHF) and medium‐size (6‐311++G** B3LYP) ab initio calculations, complete conformational libraries, containing as many as 27 conformers, have been determined for diamide model systems incorporating the amino acids valine (Val) and phenylalanine (Phe). Conformational and energetic properties of these libraries were analyzed. For example, significant correlation was found between relative energies from 6‐311++G** B3LYP and single‐point B3LYP/6‐311++G**//RHF/3‐21G calculations. Comparison of populations of molecular conformations of hydrophobic aromatic and nonaromatic residues, based on their ab initiorelative energies, with their natural abundance indicates that, at least for the hydrophobic core of proteins, the conformations of Val (Ile, Leu) and Phe (Tyr, Trp) are controlled by the local energetic preferences of the respective amino acids. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 732–751, 2001     

Zn2+‐Complexation by a β‐Peptidic Helix and Hairpin Containing β3hCys and β3hHis Building Blocks: Evidence from CD Measurements. Preliminary Communication

Two new β³‐homohistidine‐ and β³‐homocysteine‐containing β‐peptides have been prepared by solid‐phase synthesis. A β‐octapeptide ( 2 ) contains seven β³‐amino acids and one β²‐amino acid. The β²/β³ segment has been placed in the middle of this peptide, which contains β³‐amino acids of alternating configuration, to induce the formation of a hairpin secondary structure. A β‐decapeptide ( 3 ) has been designed to fold to a 3₁₄‐helical secondary structure with neighboring His side chains in 6‐ and 9‐positions. Circular‐dichroism (CD) measurements show the capability of both peptides to bind Zn²⁺ ions in aqueous solution. In the case of the β‐octapeptide, binding of Zn²⁺ causes a dramatic change of the CD spectrum, indicating a change or a stabilization of its secondary structure. Zn²⁺ Ions clearly stabilize the 3₁₄‐helix of the β‐decapeptide, in neutral and basic solution. For the construction of the two new β‐peptides, we needed to have a supply of the β‐amino acid derivatives Fmoc‐β³hCys(Trt)‐OH and Fmoc‐β³hHis(Trt)‐OH, the preparation of which is described herein.