摘要:

AbstractConformational investigations have been undertaken on oligomers (dimers, tetramers, hexamers) of five closely related oxetane‐based dipeptide isosteres. All the oligomers were subjected to a range of studies by NMR, FT‐IR and CD spectroscopy. The oligomers derived from methyl 2,4‐anhydro‐5‐azido‐3‐O‐tert‐butyldimethylsilyl‐5‐deoxy‐L‐rhamnonate ‘monomer’ all exhibited evidence of ordered conformations in chloroform and 2,2,2‐trifluoroethanol (TFE) solution. 5‐Acetamido andN‐methylamide derivatives of theL‐rhamnonate ‘monomer’, along with a ‘dimer’ lacking silyl protection at C‐3, were synthesized to ascertain the role of intramolecular interactions. This led to the conclusion that, for theL‐rhamnonate oligomers, steric interactions govern the conformational preference observed. The equivalent silyl‐protectedD‐lyxonate oligomers gave ordered CD spectra in TFE solution, but NMR and FT‐IR spectroscopy in chloroform solution suggested an irregular, non‐hydrogen bonded system. The remaining silyl‐protected 6‐deoxy‐L‐altronate, 6‐deoxy‐D‐gulonate andD‐fuconate oligomers appear to be characterized by their lack of ordered conformation in TFE and chloroform sol

ISSN:1075-2617    

DOI:10.1002/psc.658

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractA rapid and efficient strategy has been developed for the general synthesis of complex peptide aldehydes.Nα‐Benzyloxycarbonylamino acids were converted to protected aldehyde building blocks for solid‐phase synthesis in four steps and moderate overall yields. The aldehydes were protected as 1,3‐dioxolanes except for one case where a dimethyl acetal was used. These protected amino aldehyde monomers were then incorporated onto 5‐[(2 or 4)‐formyl‐3,5‐dimethoxyphenoxy]butyryl‐resin (BAL‐PEG‐PS) by reductive amination, following which the penultimate residue was introduced by HATU‐mediated acylation. The resultant resin‐bound dipeptide unit, anchored by a backbone amide linkage (BAL), was extended further by routine Fmoc chemistry procedures. Several model peptide aldehydes were prepared in good yields and purities. Some epimerization of theC‐terminal residue occurred (10% to 25%), due to the intrinsic stereolability conferred by the aldehyde functional group, rather than any drawbacks to the synthesis procedure. Copyright © 2005 European Peptide Socie

ISSN:1075-2617    

DOI:10.1002/psc.614

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractThe interactions of poly‐L‐glutamic acid and a cationic porphyrin derivative in aqueous solutions were studied by the combination of vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopies. It was found that non‐covalent interactions between both agents influence the structure of the polymeric matrix and the guest porphyrins andvice versa, but the physico‐chemical properties of the solutions, especially the pH and the relative permittivity of the solvent, play a key role in the structure of the polypeptide part of the formed complexes. It was shown that the interaction with porphyrins prevents the precipitation of poly‐L‐glutamic acid in aqueous solution at acidic pH. In special conditions, the porphyrins attached to the polypeptide probably possess face‐to‐face interaction as demonstrated by the enhancement of the characteristic ECD signal and the appearance of sidebands on its short and long wavelength sides. Copyright © 2005 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.672

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractThe FTIR spectra were analysed in the region of the νs(NH), AI(CO) and νs(CαCβ) bands for a series of Ac‐ΔXaa‐NMe2, where ΔXaa = ΔAla, (Z)‐ΔAbu, (Z)‐ΔLeu, (Z)‐ΔPhe and ΔVal, to determine a predominant solution conformation of these α,β‐dehydropeptide‐related molecules. Measurements were taken in CCl4, DCM and MeCN solutions. In the same way, spectra of saturated analogues Ac‐Xaa‐NMe2, where Xaa = Ala, Abu, Leu, Phe and Val, were investigated. To help interpret the spectroscopic results, conformational maps were calculated by the B3LYP/6–31+G** method. Also, the relative energies of all conformers of the dehydro compoundsin vacuoas well as in the studied solvents in addition to the theoretical IR frequencies of these conformers were calculated. For comparison, molecules of two saturated analogues, Ac‐L‐Ala‐NMe2and Ac‐L‐Phe‐NMe2, were calculated in a similar way. Both unsaturated and saturated compounds, which have an aliphatic side chain, occur in CCl4and DCM mainly as a mixture of extended conformers with the C5H‐bond and open conformers. As solvent polarity increases, participation of the open conformers also increases, and in MeCN, the model amides are almost exclusively in the open form, except Ac‐ΔAla‐NMe2, which shows a small amount of the H‐bonded conformer. Ac‐ΔAla‐NMe2and Ac‐ΔAbu‐NMe2have stronger C5hydrogen bonds than those of their saturated counterparts. As the calculations indicate, the open conformation of the unsaturated amides is conformer H/F with ϕ, ψ −44 ± 5°, 127 ± 4°. This is the second lowest in energy conformerin vacuoand in CCl4and the lowest one in more polar solvents. The open conformation of Ac‐L‐Ala‐NMe2constitutes conformer C with ϕ, ψ −101.5°, 112.7°. For Ac‐ΔAla‐NMe2and Ac‐ΔAbu‐NMe2, FTIR also reveals the presence of a third conformer. Calculations indicate that is the semiextended conformer D with the N1‐H1···N2hydrogen bond/contact. In all solvents, Ac‐L‐Phe‐NMe2and Ac‐(Z)‐ΔPhe‐NMe2show only the extended E and the open H/F, respecti

ISSN:1075-2617    

DOI:10.1002/psc.655

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractThe SPPS methodology has continuously been investigated as a valuable model to monitor the solvation properties of polymeric materials. In this connection, the present work applied HRMAS‐NMR spectroscopy to examine the dynamics of an aggregating peptide sequence attached to a resin core with varying peptide loading (up to 80%) and solvent system. Low and high substituted BHAR were used for assembling the VQAAIDYING sequence and some of its minor fragments. The HRMAS‐NMR results were in agreement with the swelling of each resin, i.e. there was an improved resolution of resonance peaks in the better solvated conditions. Moreover, the peptide loading and the attached peptide sequence also affected the spectra. Strong peptide chain aggregation was observed mainly in highly peptide loaded resins when solvated in CDCl3. Conversely, due to the better swelling of these highly loaded resins in DMSO, improved NMR spectra were acquired in this polar aprotic solvent, thus enabling the detection of relevant sequence‐dependent conformational alterations. The more prominent aggregation was displayed by the VQAAIDYING segment and not by any of its intermediary fragments and these findings were also corroborated by EPR studies of these peptide‐resins labelled properly with an amino acid‐type spin probe. Copyright © 2005 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.659

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractRelaxin is a member of the insulin superfamily and has many biological actions including angiogenesis and collagen degradation. It is a 6 kDa peptide hormone consisting of two peptide chains (A and B) tethered by two disulphide bonds. Past structure–function relationship studies have shown the key receptor binding site of relaxin to be principally situated within the B‐chain α‐helix. Molecular dynamic simulations were performed to aid the design of conformationally constrained relaxin B‐chain analogues that possess α‐helical structure and relaxin‐like activity. Restraints included disulphide bonds, both single and double, and lactam bonds. Each peptide was prepared by solid phase synthesis and, following purification, subjected to detailed conformational analysis by circular dichroism spectroscopy. Of 15 prepared relaxin B‐chain mimetics, one was able to mimic the secondary structure of the native ligand as indicated by biomolecular recognition/interaction analysis using surface enhanced laser desorption ionization mass spectroscopy together with a relaxin antibody. However, none of the mimetics possess characteristic relaxin‐like biological activity which strongly indicates that the pharmacophore comprises additional structural elements other than the relaxin B‐chain α‐helix. These findings will assist in the design and preparation of novel relaxin agonists and antagonists. Copyright © 2005 European Peptide Society a

ISSN:1075-2617    

DOI:10.1002/psc.652

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractA new safety‐catch linker for Fmoc solid‐phase peptide synthesis of cyclic peptides is reported. The linear precursors were assembled on atert‐butyl protected catechol derivative using optimized conditions for Fmoc‐removal. After activation of the linker using TFA, neutralization of theN‐terminal amine induced cyclization with concomitant cleavage from the resin yielding the cyclic peptides in DMF solution. Several constrained cyclic peptides were synthesized in excellent yields and purities. Copyright © 2005 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.651

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractThe synthesis ofp‐nitrophenoxycarbonyl derivatives of 1‐Boc‐1,2‐diaminoethane, 1‐Boc‐1,3‐diaminopropane and 1‐Boc‐1,4‐diaminobutane is described. These derivatives were used to synthesize five peptidomimetics, analogues of enkephalin, containing alkylurea units inside the peptide chain and at theC‐terminal. All syntheses were carried out in solid phase on MBHA resin. Peptidomimetics with alkylurea units inserted into the peptide chain were synthesized using the standard method employing the Boc‐strategy, with TFA deprotection and HF cleavage. The analogue containing aC‐terminal alkylurea unit was synthesized using the Boc‐strategy, with HCl/dioxane deprotection and TFA cleavage. All of the analogues were examined for opioid activity in GPI and MVD assays. The activity of the analogue containing aC‐terminal alkylurea unit was comparable to that of [Leu5]‐enkephalin, while the other analogues were less active. Copyright © 2005 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.650

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractThis study describes the synthesis and some pharmacological properties of eight new analogues of arginine vasopressin (AVP) substituted at position 2 or 3 with cycloleucine (1‐aminocyclopentane‐1‐carboxylic acid, Apc). All new peptides were tested for their pressor, antidiuretic and uterotonicin vitropotency. The Apc3modification resulted in an almost complete loss of potency in all three tests, which is interpreted as a loss of interaction with all three neurohypophyseal hormone receptors. On the other hand, the Apc2modification resulted in compounds having differently modified activities (high antidiuretic potency, low and graded pressor activity and either no activity or low oxytocin antagonizing activity in the uterotonicin vitrotest) thus selectively altering the interaction with the receptors similar to that of 1‐aminocyclohexane‐1‐carboxylic acid (Acc). The results obtained may be helpful for designing new analogues of arginine vasopressin. Copyright © 2005 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.656

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractPhytosulfokine‐α (PSK‐α), a sulfated growth factor of structure H‐Tyr(SO3H)‐Ile‐Tyr(SO3H)‐Thr‐Gln‐OH universally found in both monocotyledons and dicotyledons, strongly promotes proliferation of plant cells in culture. In studies on the structure/activity relationship of PSK‐α the synthesis was performed of a series of a further 23 analogues modified in position 1, 3 or 4 as well as simultaneously in positions 1 and 3 of the peptide chain. Peptides were synthesized by the solid phase method according to the Fmoc procedure on a Wang‐resin. Free peptides were released from the resin by 95% TFA in the presence of EDT. All peptides were tested by competitive binding assay to the carrot membrane using3H‐labelled PSK‐α according to the test of Matsubayashiet al. Among these peptide analogues, [H‐Phe(4‐Cl)1]‐PSK‐α (IV), [H‐Phe(4‐I)1]‐PSK‐α (VII), and [Phe(4‐Cl)3]‐PSK‐α (XI) retained 30% PSK‐α activity. Analogue [Tyr(PO3H2)3]‐PSK‐α (IX) showed 10% of PSK‐α activity. Cop

ISSN:1075-2617    

DOI:10.1002/psc.653

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY