Heterotrimeric collagen peptides containing functional epitopes. Synthesis of single‐stranded collagen type I peptides related to the collagenase cleavage site

Synthetic collagen peptides containing larger numbers of Gly‐Pro‐Hyp repeats are difficult to purify by standard chromatographic procedures. Therefore, efficient strategies are required for the synthesis of higher molecular weight collagen‐type peptides. Applying the Fmoc/tBu chemistry, a comparative analysis of the standard stepwise chain elongation procedure on solid support with the procedure based on the use of the synthons Fmoc‐Gly‐Pro‐Hyp(tBu)‐OH and Fmoc‐Pro‐Hyp‐Gly‐OH was performed. The crude products resulting from the stepwise elongation procedure and from the use of Fmoc‐Gly‐Pro‐Hyp(tBu)‐OH clearly revealed large amounts of microheterogeneities that result from incomplete imino acid acylation as well as from diketopiperazine formation with cleavage of Gly‐Pro units from the growing peptide chain. Conversely, by the use of the Fmoc‐Pro‐Hyp‐Gly‐OH synthon, the quality of the crude products was significantly improved; moreover, protection of the Hyp side chain hydroxyl function is not required using the Fmoc/tBu strategy. With this optimized synthetic procedure, relatively large collagen‐type peptides were obtained in satisfactory yields as highly homogeneous compounds. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.     

Innovative chemical synthesis and conformational hints on the lipopeptide liraglutide

Liraglutide is a new generation lipopeptide drug used for the treatment of type II diabetes. In this work, we describe new approaches for its preparation fully by chemical methods. The key step of these strategies is the synthesis in solution of the Lys/γ‐Glu building block, Fmoc‐Lys‐(Pal‐γ‐Glu‐OtBu)‐OH, in which Lys and Glu residues are linked through their side chains and γ‐Glu is N^α‐palmitoylated. This dipeptide derivative is then inserted into the peptide sequence on solid phase. As liraglutide is obtained with great purity and high yield, our approach can be particularly attractive for an industrial production. We also report here the results of a circular dichroism conformational analysis in a membrane mimetic environment that offers new insights into the mechanism of action of liraglutide. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.     

Comparison of the stepwise and convergent approaches in the solid-phase synthesis of rat Tyr0-atriopeptin II

Summary Tyr^o-Atriopeptin II was synthesized on a 2-chlorotrityl resin by both, the stepwise and the convergent approach. For both methods an Fmoc/tBu(Trt)-based protection scheme was used. The convergent methodology utilizes the sequential condensation of four protected peptide fragments. These were chosen so that after every condensation reaction, the amino-terminal region of the newly formed resin-bound peptide did not contain a β-turn. This ‘designed’ convergent synthesis gave the target peptide in much higher yield and purity than the conventional stepby-step synthesis. HOAc, acetic acid; Boc,tert-butyloxycarbonyl; DCC, dicyclohexylcarbodiimide: DCM, dichloromethane; DIC, diisopropylcarbodiimide; DIEA,N,N-diisopropylethylamine; DMFN,N-dimethylformamide; DMSO, dimethylsulfoxide; EDT. ethanedithiol; FAB-MS, fast atom bombardment mass spectrometry; Fmoc, 9-luorenylmethoxycarbonyl; HOBt, 1-hydroxybenzotriazole; HPLC, high-performance liquid chromatography; i-PrOH, isopropanol; Mmt, 4-methoxytrityl; PEG-PS, polvethyleneglycol grafted polystyrene; Pme, 2,2,5,7,8-pentamethylchroman-6-sulfonyl; RP, reversed phase; rt, room temperature; SPPS, solid phase peptide synthesis;tBu,tert-butyl; TFA, trifluoroacetic acid; TFE, trifluoroethanol; TLC, thin layer chromatography; Trt, triphenylmethyl, trityl. Abbreviations used for amino acids follow the rules of the IUPAC-IUB Commission of Biochemical Nomenclature [J. Biol. Chem. 247 (1972), 977]. All amino acids are of the L-configuration.     

An HPLC‐ESMS study on the solid‐phase assembly of C‐terminal proline peptides

DKP formation is a serious side reaction during the solid‐phase synthesis of peptide acids containing either Pro or Gly at the C‐terminus. This side reaction not only leads to a lower overall yield, but also to the presence in the reaction crude of several deletion peptides lacking the first amino acids. For the preparation of protected peptides using the Fmoc/tBu strategy, the use of a ClTrt‐Cl‐resin with a limited incorporation of the C‐terminal amino acid is the method of choice. The use of resins with higher loading levels leads to more impure peptide crudes. The use of HPLC‐ESMS is a useful method for analysing complex samples, such as those formed when C‐terminal Pro peptides are prepared by non‐optimized solid‐phase strategies. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.     

Microwave Assisted Alcoholysis of Isocyanates Derived from N<Superscript>α</Superscript>-[(9-fluorenylmethyl)oxy]carbonyl Amino Acids: Synthesis of N-Fmoc-N<Superscript>1</Superscript>-Z-/Boc-/Alloc-/Bsmoc-gem-diamines

A general and efficient method has been developed for the alcoholysis of isocyanates derived from the N^α-[(9-fluorenylmethyl)oxy]carbonyl amino acids with various alcohols including hindered ones assisted by MW irradiation. Thus, the synthesis of N, N¹-diurethane protected gem-diamines wherein Fmoc protection on one of the amino groups and Z-/Boc-/Alloc or Bsmoc group on the other amino function has been accomplished. All the new orthogonally diurethane protected gem-diamines have been obtained as crystalline solid powders in 80 to 94% yield. The bisprotected gem-diamines have been fully characterized by IR, ¹H NMR, ¹³C NMR as well as by mass spectrometry.     

Synthesis of cyclic herpes simplex virus peptides containing 281–284 epitope of glycoprotein D‐1 in endo‐ or exo‐position

We have prepared two types of cyclopeptides containing the ²⁸¹DPVG²⁸⁴ sequence from the 276–284 region of glycoprotein gD‐1 of the Herpes simplex virus (HSV). The syntheses were performed by solid phase methodology using MBHA or BHA resin and orthogonal protection schemes. Head‐to‐side‐chain cyclization included the N‐terminal part of the epitope, while side‐chain‐to‐side‐chain lactam bridge formation resulted in a peptide containing a C‐terminal cycle. Peptides elongated by Cys at the N‐terminal of the sequence were also prepared. Boc chemistry using Fmoc and OFm orthogonal protection was applied for on‐resin cyclization. Based on the orthogonality of Bzl and cHex esters under a 1 m TMSOTf‐thioanisole/TFA cleavage condition, a new approach for the cyclization on BHA‐resin has also been developed. Preliminary studies on solution conformation of the cyclic peptides by CD spectroscopy indicated the importance of the location and the size of the cycle within the epitope sequence. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.     

Sequence dependence of aspartimide formation during 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis

Summary We have examined the sequence dependence of aspartimide formation during Fmoc-based solid-phase synthesis of the peptide Val-Lys-Asp-X-Tyr-Ile. The extent of aspartimide formation and subsequent conversion to the - or -piperidide was characterized and quantitated by analytical reversed-phase high-performance liquid chromatography and fast atom bombardment mass spectrometry. Aspartimide formation occurred for X=Arg(Pmc), Asn(Trt), Asp(OtBu), Cys(Acm), Gly, Ser, Thr and Thr(tBu). No single approach was found that could inhibit this side reaction for all sequences. The most effective combinations, in general, for minimization of aspartimide formation were (i) tert-butyl side-chain protection of aspartate, piperidine for removal of the Fmoc group, and either 1-hydroxybenzotriazole or 2,4-dinitrophenol as an additive to the piperidine solution; or (ii) 1-adamantyl side-chain protection of aspartate and 1,8-diazabicyclo[5.4.0]undec-7-ene for removal of the Fmoc group.     

Synthesis and characterization of organotin Schiff base chelates

The synthesis and characterization of five organotin compounds containing Salophen(^tBu) [Salophen(^tBu)=N,N′-phenylene-bis(3,5-di-tert-butylsalicylideneimine)], Salomphen(^tBu) [Salomphen(^tBu)=N,N′-(4,5-dimethyl)phenylene-bis(3,5-di-tert-butylsalicylideneimine)] and Phensal(^tBu) [Phensal(^tBu)=3,5-di-tert-butylsalicylidene(1-aminophenylene-2-amine)] ligands is described. These compounds include the monomeric complexes LSnCl₂ (where L=Salophen(^tBu), L=Salomphen(^tBu)), L(ⁿBu)SnCl (where L=Salophen(^tBu), Salomphen(^tBu)), L(ⁿBu)SnCl₂ (where L=Phensal(^tBu)). Spectroscopic techniques including ¹¹⁹Sn NMR and X-ray crystallography were used in the characterization of the compounds.     

The synthesis and use of pp60-related peptides and phosphopeptides as substrates for enzymatic phosphorylation studies

A series of peptides and phosphopeptides corresponding to the auto-phosphorylation site of pp60^src, -Asn-Glu-Tyr⁴¹⁶-Thr-Ala-, were prepared by either Boc/solution or Fmoc/solid phase peptide synthesis and used as substrates to study their enzymatic phosphorylation by various casein kinases. The Tyr(P)-containing peptide, Asn-Glu-Tyr(P)-Thr-Ala, was prepared by the use of Fmoc-Tyr(PO₃Bzl₂)-OH in Fmoc/solid phase peptide synthesis followed by acidolytic treatment of the peptide-resin with 5% anisole/CF₃CO₂H. Both Asn-Glu-Tyr-Thr-Ala and Asn-Glu-Ser(P)-Thr-Ala were prepared by the Boc/solution phase peptide synthesis and employed hydrogenolytic deprotection of the protected peptides. Enzymatic phosphorylation studies established that (A) the Tyr residue acted as an unusual positive determinant for directing phosphorylation to the Thr-residue, (B) the rate of Thr-phosphorylation was markedly facilitated by a change from the Tyr-residue to the Tyr(P)-residue, and (C) a Ser(P)-residue was as effective as the Tyr(P)-residue in facilitating Thr-phosphorylation. A subsequent structure-function study using Asn-Glu-Phe-Thr-Ala, Asn-Glu-Tyr(Me)-Thr-Ala (prepared by Fmoc/solid phase peptide synthesis) and Asn-Glu-Cha-Thr-Ala (prepared by hydrogenation of Asn-Glu-Tyr-Thr-Ala) established that the rate of Thr-phosphorylation was influenced by the extent of hydrophobic-hydrophobic interactions by the aralkyl side-chain group (either aromatic or aliphatic) of the 416-residue with casein kinase-2; the rate of Thr-phosphorylation being decreased by the introduction of methyl or hydroxyl groups at the 4-position of the aromatic group {i.e. Tyr(Me) and Tyr respectively} but enhanced by the introduction of the hydrophilic phosphate group {i.e. as Tyr(P)}.     

Synthesis, structural studies and solubility properties of zinc(II), nickel(II) and copper(II) complexes of bulky tris(triazolyl)borate ligands

Tris(triazolyl)borate (Ttz) ligands are sterically similar to tris(pyrazolyl)borate (Tp) but complexes of Ttz show improved solubility in water and alcohols due to their propensity for forming hydrogen bonds. Recently developed bulky tris(triazolyl)borate ligands can produce four and five coordinate transition metal complexes and serve as models for enzyme active sites in an aqueous environment. Herein we report the synthesis of such complexes, i.e. (Ttz^tBu,Me)ZnCl, (Ttz^tBu,Me)ZnBr, (Ttz^tBu,Me)NiCl, and (Ttz^tBu,Me)CuCl, which were analyzed by X-ray crystallographic and spectroscopic methods [Ttz^tBu,Me = tris(3-t-butyl-5-methyl-1,2,4-triazolyl)borate]. (Ttz^tBu,Me)ZnCl crystallizes as two different polymorphs with cubic and monoclinic symmetry. Both polymorphs of (Ttz^tBu,Me)ZnCl and (Ttz^tBu,Me)ZnBr have tetrahedral zinc atoms whereas the geometries at the metal in (Ttz^tBu,Me)NiCl and (Ttz^tBu,Me)CuCl are distorted tetrahedral. All complexes are methanol soluble and they also dissolve in methanol/water mixtures with up to 60% water.     

Synthesis and reactivity of imido niobium complexes containing the functionalized (dichloromethylsilyl)cyclopentadienyl ligand

The niobium complex [NbCp^ClCl₄] (Cp^Clη⁵-C₅H₄(SiCl₂Me)) (1) with a functionalized (dichloromethylsilyl)cyclopentadienyl ligand was isolated by the reaction of [NbCl₅] with C₅H₄(SiCl₂Me)(SiMe₃). Complex 1 was a precursor for the imido silylamido derivative [NbCp^NCl₂(NtBu)] (Cp^Nη⁵-C₅H₄[SiClMe(NHtBu)]) (2) after addition of LiNHtBu, which subsequently gave the dichlorosilyl compound [NbCp^ClCl₂(NtBu)] (3) when reacted with SiCl₃Me. Addition of LiNHtBu to complex 2 gave the niobium amido complex [NbCp^NCl(NHtBu)(NtBu)] (4), which slowly evolved with exchange of the niobium-amido and the silicon-chloro groups to give the dichloroniobium complex [NbCp^NNCl₂(NtBu)] (Cp^NNη⁵-C₅H₄[SiMe(NHtBu)₂]) (5). Reaction of 2 with excess LiNHtBu gave the silyl-η-amido constrained geometry complexes [Nb{η⁵-C₅H₄[SiMe(NHtBu)(-η-NtBu)]}(NHtBu)(NtBu)] (6) and [Nb{η⁵-C₅H₄[SiClMe(-η-NtBu)]}(NHtBu)(NtBu)] (7), whereas addition of one equimolecular amount of LiNHtBu to 5 in C₆D₆ afforded complex [NbCp^NNCl(NHtBu)(NtBu)] (8). All of the new complexes were characterized by ¹H, ¹³C and ²⁹Si NMR spectroscopy.     

Epitope mapping of the N‐terminal portion of tissue transglutaminase protein antigen to identify linear epitopes in celiac disease

Celiac disease (CD) is an autoimmune mediated disease with complex and multifactorial etiology. Gluten intake triggers a composite immune response involving T‐cells and B‐cells and leading to the secretion of autoantibodies if a genetic predisposition is present. Untreated CD patients show high levels of circulating autoantibodies directed to different auto‐antigens present in the intestinal mucosa. The most important auto‐antigen is the endomysial enzyme tissue transglutaminase (tTG). Both IgA and IgG antibody isotypes to tTG are known, but only the IgA antibodies demonstrate the highest disease specificity and thus are considered disease biomarkers. Because the pathogenicity and exact tTG binding properties of these autoantibodies are still unclear, the characterization of tTG antigenic domains is a crucial step in understanding CD onset and the autoimmune pathogenesis. Overlapping peptide libraries can be used for epitope mapping of selected protein portions to determine antigenic fragments contributing to the immunological activity and possibly develop innovative peptide‐based tools with high specificity and sensitivity for CD. We performed an epitope mapping study to characterize putative linear auto‐antigenic epitopes present in the tTG N‐terminal portion (1–230). A library of 23 overlapping peptides spanning tTG(1–230) was generated by Fmoc/tBu solid‐phase peptide synthesis and screened by immunoenzymatic assays employing patients' sera. The results indicate that four synthetic peptides, that is, Ac‐tTG(1–15)‐NH₂, Ac‐tTG(41–55)‐NH₂, Ac‐tTG(51–65)‐NH₂, and Ac‐tTG(151–165)‐NH₂, are recognized by IgA autoantibodies circulating in CD patients' sera. These results offer important insight on the nature of the antigen‐antibody interaction. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Stability of the O-octanoyl group of rat ghrelin during chemical synthesis: Counter-ion-dependent alteration of an ester bond breakage

Summary Rat ghrelin, a 28-amino acid residue peptide with an octanoyl group at the side chain of Ser3, was synthesized chemically by applying Fmoc/ ^t Bu strategy. An ester linkage between octanoic acid and the hydroxyl function of Ser3 was found to be maintained without serious damage during the final deprotection with trifluoroacetic acid (TFA). The most notable finding was the counter-ion-dependent stability change of the octanoyl moiety in the molecule. After consolidation of the counter-ion to TFA (TFA form), the octanoyl group persisted stably upon dissolution in water, whereas in the case of the acetate-form peptide, both de-octanoylation and dehydration (formation of the dehydro-Ala residue) occurred in aqueous solution at the same Ser3 residue. The amounts of these degraded products varied with factors such as solvent, temperature and times of lyophilization. These experimental findings lay the basis for performing the bioassay of ghrelin, which has an octanoyl moiety involved in its numerous biological activities thus far revealed.     

Preparation, structure, solid state and gas phase stability of the mixed neodymium nitrate-chloride complex NdCl(NO3)2{[(MeO)2PO]2C(OH)Bu}2

The preparation and structure of the mixed anion complex NdCl(NO₃)₂{[(MeO)₂PO]₂C(OH)^tBu}₂ are reported. Single crystal X-ray diffraction shows that the bisphosphonate is bonded via both phosphoryl groups and the nitrates act as bidentate ligands. Intramolecular H-bonding is seen between the OH and the coordinated nitrate and chloride ligands. Thermal decomposition in the solid state is by loss of methyl nitrate. Electrospray mass spectrometry shows that loss of chloride is preferred over loss of nitrate in the gas phase. Attempted preparation of NdCl₂(NO₃){[(MeO)₂PO]₂C(OH)^tBu}₂ leads to the formation of a product approximating to [Nd{^tBu(OH)C(PO₃H₂)₂}₂]₂H · NO₃ · (PO₄H₂)₂. Electrospray mass spectrometry and elemental analysis confirm the presence of the [^tBu(OH)C(PO₄H₂)₂]⁻ in the decomposition products.     

Reductive C-N bond cleavage of the NCCCN β-diketiminate backbone: A direct approach to azabutadienyl and alkylidene-anilide scaffolds

Tetrahydrofuran/toluene solutions of (nacnac)TiCl₂ (nacnac⁻ = [ArNC(^tBu)]₂CH, Ar = 2,6-ⁱPr₂C₆H₃) react readily with KC₈ to afford the titanium imide (ArN(^tBu)CCHC(^tBu))TiNAr(THF)Cl (1) in 67% isolated yield. Complex 1 forms from the two-electron reductive C-N bond cleavage of the β-diketiminate ligand. Likewise, reduction of (nacnac)TiCl(NHAr) (2), prepared in 85% yield from (nacnac)TiCl₂ and LiNHAr, with KC₈ results in formation of the imide-anilide analogue (ArN(^tBu)CCHC(^tBu))TiNAr(NHAr) (3) in 88% yield. Another reductant such as Li^tBu (3 equiv.) reacts cleanly with the precursor (nacnac)TiCl₂ to afford the alkylidene-ate complex [Li(Et₂O)][(ArN(^tBu)CCHC(^tBu))TiNAr(Et₂O)] (4), in 81% yield. Complexes 1-4 have been characterized by ¹H and ¹³C NMR spectra as well as single-crystal X-ray diffraction analysis. Plausible mechanisms to formation of compounds 1, 3 and 4 are also presented and discussed.     

Fmoc chemistry compatible thio-ligation assembly of proteins

We describe, and compare, two methods which enable theassembly of proteins from peptide thioester fragmentsprepared by Fmoc chemistry mediated solid phase synthesis. The first, which utilizes iso-thiouronium salts,allows formation of thiophenyl esters directly frompartially protected peptides, either in solution or onresin. The second uses sulfonamide based safety-catchresins. Data on yields, generality and potential for side-reactions are provided.     

Enlarging the family of ferrocenylphosphine dinuclear rhodium complexes: synthesis and X-ray structure of a novel “A-frame”-type trimetallic Rh/Fe/Rh complex

The symmetrically substituted ligand 1,1^′-bis[di(5-methyl-2-furyl)phosphino]ferrocene (1) has been obtained from the bromophosphine BrP(Fu^Me)₂ and the dilithioferrocene/TMEDA adduct. The quantitative addition of this ferrocene derivative to the tetracarbonyl dimer [(CO)₄Rh₂{μ-(S^tBu)₂}] leads, through decarbonylation, to the dinuclear rhodium complex [(CO)₂Rh₂{μ-(S^tBu)₂}{μ-P,P-Fc[P(Fu^Me)₂]₂}] (2) in high yield. A X-ray structure [orthorhombic, space group P2₁2₁2₁; a=11.2982(2) Å, b=13.3165(3) Å, c=27.2687(7) Å] and the solution multinuclear NMR characterization are reported, which show that the rare “quasi-closed bridging” A-frame structure of the complex is rather similar to the one reported for [(CO)₂Rh₂{μ-(S^tBu)₂}{μ-P,P-dppf}] in solid state. However, in solution the furyl-containing ferrocenylphosphine complex presents a greater fluxionality, together with an electronic environment at phosphorus very different from the dppf analogue (δ_P=−10 and 27 ppm, respectively).     

Trans-cis amide bond isomerization in fulleroprolines

The ¹H NMR study of fulleroproline derivative Ac-Fpr-OtBu and its Pro analogue Ac-l -Pro-OtBu over a range of temperatures in toluene-d₈ solution has enabled the comparison of their equilibrium and activation parameters for the trans/cis interconversion around the amide partial double bond. © 1998 European Peptide Society and John Wiley & Sons, Ltd.     

Solution phase synthesis of the 14-residue peptaibol antibiotic trichovirin I

Summary.  The 14-residue peptaibol antibiotic trichovirin I 4A of the structure Ac-Aib-L-Asn-L-Leu-Aib-L-Pro-L-Ala-L-Val-Aib-L-Pro-Aib-L-Leu-Aib-L-Pro-L-Leuol (Aib = α-aminoisobutyric acid, Leuol = leucinol) was synthesized by stepwise conventional solution phase synthesis using the Z/OtBu(OMe) strategy and HOBt/EDC as coupling reagents. Intermediates were fully characterized and the identity of the synthetic peptide with the component 4A of the natural, microheterogeneous peptide mixture was proven by electrospray mass spectrometry, HPLC, and bioassay. Received March 25, 2002 Accepted June 14, 2002 Published online December 18, 2002 RID="*" ID="*"  Dedicated to Prof. Dr. Günther Jung. Tübingen University, on the occasion of his 65^th anniversary. Authors' address: Prof. Dr. Hans Brückner, Interdisciplinary Research Center, Institute of Nutritional Science, Department of Food Sciences, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26, D-35392 Giessen, Germany, Fax: +49-641-99-39149, E-mail: hans.brueckner@ernaehrung.uni-giessen.de Abbreviations: Amino acids are abbreviated according to three-letter-nomenclature; Aib, α-aminoisobutyric acid (2-methylalanine); Iva (isovaline, 2-ethylalanine); Leuol, L-leucinol [(S)-2-amino-4-methyl-1-pentanol]; AAA, amino acid analysis; EI-MS, electron impact mass spectrometry; ESI-MS, electrospray ionization mass spectrometry; HPLC, high performance liquid chromatography; Z, benzyloxycarbonyl; Fmoc, 9-fluorenylmethyoxycarbonyl; OtBu, tertiary butoxy (tert-butylester); OMe, methoxy (methyl ester); OBzl, benzyloxy (benzyl ester); TDM, N,N,N′,N′-tetramethyl-4,4′-diamino-diphenylmethane (Arnold's base); for other abbreviations see Experimental.     

The crystal state conformation of Aib-rich segments of peptaibol antibiotics

Ac-(Aib-Ala)₃-OH (a protected segment of the peptaibols gliodeliquescin and paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of [Leu]⁷-gliodeliquescin), Z-Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsin, and hypelcin), and Ac-Aib-Pro-(Aib-Ala)₂-OMe and Z-Aib-Pro-(Aib-Ala)₂-OMe, which represent differently N^α-protected 1–6 segments of alamethicin and hypelcin, have been synthesized by solution methods. The crystal-state conformations of these five Aib-containing peptides have been determined by X-ray diffraction analysis. We have confirmed that the 3₁₀-helical structure is preferentially adopted by Aib-rich short peptides. An experimentally unambiguous proof for the 3₁₀→α-helix conversion has been provided by the two differently N-blocked -Aib-Pro-(Aib-Ala)₂-OMe hexapeptides. The β-bend ribbon conformation, commonly observed in the (Aib-Pro)_n sequential oligopeptides, is not found in the -Aib-Pro-Aib-Ala-Aib-Ala- sequence. As expected on the basis of the l -configuration of the C^α-monoalkylated residues, a right-handed helix screw sense was found in all peptides investigated. © 1998 European Peptide Society and John Wiley & Sons, Ltd.