摘要:

AbstractN‐benzyloxycarbonyl‐protected α‐ or β‐amino alcohols, easily prepared from α‐ and β‐amino acids, were converted into aldehydes and directly reacted with (triphenyl phosphoranylidene) acetonitrile, leading to unsaturated nitriles. Treatment of nitriles with NaN3and ZnBr2produced unsaturated γ‐ and δ‐amino tetrazoles, which were deprotected and converted to the corresponding saturated compounds by catalytic hydrogenation. For the case of δ‐amino tetrazole, the methylation of the acidic moiety occurred after treatment with CH2N2, leading to theN1‐ andN2‐methylated constitutional isomers, which were separated by column chromatography and hydrogenated. Copyright © 2006 European Peptide Soc

ISSN:1075-2617    

DOI:10.1002/psc.737

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractThe recently isolated broad‐spectrum antiparasitic apicidin (1) is one of the few naturally occurring cyclic tetrapeptides (CTP). Depending on the solvent, the backbone of1exhibits two γ‐turns (in CH2Cl2) or a β‐turn (in DMSO), differing solely in the rotation of the plane of one of the amide bonds. In the X‐ray crystal structure, the peptidic COs and NHs are on opposite sides of the backbone plane, giving rise to infinite stacks of cyclotetrapeptides connected by three intermolecular hydrogen bonds between the backbones. Conformational searches (Amber force field) on a truncated model system of1confirm all three backbone conformations to be low‐energy states. The previously synthesized analogs of1containing a reduced amide bond exhibit the same backbone conformation as1in DMSO, which is confirmed further by the X‐ray crystal structure of a model system of the desoxy analogs of1. This similarity helps in explaining why the desoxy analogs retain some of the antiprotozoal activities of apicidin. The backbone‐reduction approach designed to facilitate the cyclization step of the acyclic precursors of the CTPs seems to retain the conformational preferences of the parent peptide backbone. Copyright © 2005 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.738

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractGlycation of peptides and proteins is a slow chemical reaction of reducing sugars modifying the amino groups. The first intermediates of this nonenzymatic glycosylation are the Amadori products that can undergo further chemical reactions, finally leading to advanced glycation end products (AGEs). The formation of AGEs was not only linked to aging of tissues and organs in general but also to several diseases such as diabetes mellitus and Alzheimer's disease. Because of the importance of these modifications and their potential use as diagnostic markers, a global postsynthetic approach on solid phase was developed. The peptides were synthesized by Fmoc/tBu‐chemistry, with the lysine residue to be modified being protected with the very acid‐labile methyltrityl group. Incubation of the peptides withD‐glucose in DMF at elevated temperatures resulted in product yields of 35%. Neighboring residues with bulky protecting groups reduced the yields only slightly. The major by‐products were the unmodified peptide and an oxidation product. Whereas the unmodified peptide eluted before the glycated peptide, all other by‐products eluted later in RP‐HPLC, allowing simple purification. Copyright © 2005 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.739

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractWe synthesized three different lengths of poly(L‐lysine) containing an ‐SH group at the terminal (PLLn‐SH,n(polymerization degree) = 4, 10, 30) and adsorbed them on an Au(111) surface. To analyze the formation process and the structure of self‐assembled monolayers (SAMs), we used atomic force microscopy (AFM) and Fourier transform infrared reflection absorption spectra (FT‐IR RAS). At the initial stage of SAM growth, formation of nanosize domains was confirmed by AFM imaging. The α‐helical PLL30‐SH exhibited a well‐defined SAM structure after adsorption reached equilibrium. The α‐helical PLL30‐SH was almost perpendicular to the gold surface and exhibited interesting molecular packing due to the secondary structure of PLL30‐SH and the underlying Au(111) array. The tilt angle of the helix axis from the substrate normal was estimated to be about 50° (AFM) and 44° (FT‐IR RAS) respectively. On the other hand, PLL4‐SH and PLL10‐SH formed β‐sheet‐type SAMs on the Au(111) surface based on the structure determined by FT‐IR RAS spectrum. Copyright © 2005 European P

ISSN:1075-2617    

DOI:10.1002/psc.740

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractThe free energies of transfer for indole and tryptophan derivatives and pentapeptides having single tryptophan residues from aqueous to sodium dodecyl sulfate (SDS) micellar phases have been systematically studied using the conventional method of ultraviolet absorption spectrophotometry. The free energies for the position isomers of methyl indoles varied depending on the substitution positions. Thus, the contribution of the methyl group to the binding affinity of the 4‐methyl indole to the micelle was about twice that of the 2‐ and 7‐methyl indoles. The free energy changes with the introduction of halogen groups to the indole rings were correlated to the nonpolar water‐accessible surface area (ΔAnp) of the halogen moieties, which were regarded as hydrophobic. The relationships followed straight lines passing through the origins. Position dependence having tendencies similar to the methyl indoles was observed among the magnitudes of the slopes of the straight lines. These results strongly suggest that the indole rings of the derivatives residing in the micellar interface regions direct their imino moieties NH toward the micellar surfaces. Experiments using model tryptophan pentapeptides showed that the magnitude of free energy change per methylene unit of an alkyl amino acid residue in the pentapeptide increased with elongation of the alkyl moiety and was not a constant value as reported for various alkyl compounds. When the peptides distribute to the SDS micelles, the peptide backbones are anchored in aqueous phases and the amino acid side chains in the interfaces extend their alkyl groups toward the micellar centers. Thus, the free energy changes can be connected to the positions of the alkyl groups of the amino acid residues in the micelles. Copyright © 2005 European Peptide Society and John Wi

ISSN:1075-2617    

DOI:10.1002/psc.741

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractEleven new analogues were synthesized by modification of the potent oxytocin antagonist (OTA) [(S)Pmp1,D‐Trp2, Pen6, Arg8]‐Oxytocin, or PA (parent antagonist), in which (S)Pmp = β,β‐(3‐thiapentamethylene)‐β‐mercapto‐propionic acid. By internal acylation of Lys, Orn,L‐1,4‐diaminobutyric acid (Dab),L‐1,3‐diaminopropionic acid (Dap) at position 4 with theC‐terminal Gly of the peptide tail, we prepared cyclo‐(4–9)‐[Lys4, Gly9]‐PA (pA2= 8.77 ± 0.27), 1, and cyclo‐(4–9)‐[Orn4, Gly9]‐PA (pA2= 8.81 ± 0.25), 3, which are equipotent with PA (pA2= 8.68 ± 0.18) in the rat uterotonic assay and cyclo‐(4–9)‐[Dab4, Gly9]‐PA, 4, cyclo‐(4–9)‐[Dap4, Gly9]‐PA, 5, and cyclo‐(4–9)‐[Pmp1, Lys4, Gly9]‐PA, 2, which were weaker OTAs. Neither 1 nor 3 had activity as agonists or antagonists in the antidiuretic assay. In the pressor assay, both analogues 1 and 3, with pA2= 7.05 ± 0.10 and pA2= 6.77 ± 0.12, respectively, are somewhat weaker antagonists than PA (pA2= 7.47 ± 0.35) showing significant gain in specificity. The [desamido9] PA‐ethylenediamine monoamide, 6, and the dimer ([desamido9]‐PA)2ethylenediamine diamide, 7, had lower potency in the uterotonic assay than PA. Additionally, we synthesized cyclo‐(1–5)‐[(HN)Pmp1, Asp5]‐PA, 8, inactive in all tests, which suggests that the intact Asn5side chain may be critical in the interaction of the OTAs with the oxytocin (OT) receptor. Similarly, cyclo‐(5–9)‐[Dap5, Gly9]‐PA, 9, had very low uterotonic potency. Two derivatives of PA truncated from theC‐terminus were internally cyclized to Lys4, giving rise to cyclo‐(4–8)‐desGly‐$\hbox{NH}_{2}^{9}$[Lys4, Arg8]‐PA, 10 (pA2= 8.35 ± 0.20), which maintains the high potency of PA and has no activity in the rat antidiuretic assay, and in the rat pressor assay it is about ten times weaker (pA2 = 6.41 ± 0.15) than PA (pA2 = 7.47 ± 0.35), thus showing gains in specificity, and to cyclo‐(4–7)‐desArg‐Gly‐$\hbox{NH}_{2}^{8-9}$[Lys4, Pro7)‐PA, 11, which has much weaker potency than PA. Synthesis of cyclo‐(4–

ISSN:1075-2617    

DOI:10.1002/psc.742

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractScorpion toxins are important physiological probes for characterizing ion channels. Molecular databases have limited functional annotation of scorpion toxins. Their function can be inferred by searching for conserved motifs in sequence signature databases that are derived statistically but are not necessarily biologically relevant. Mutation studies provide biological information on residues and positions important for structure–function relationship but are not normally used for extraction of binding motifs. 3D structure analyses also aid in the extraction of peptide motifs in which non‐contiguous residues are clustered spatially. Here we present new, functionally relevant peptide motifs for ion channels, derived from the analyses of scorpion toxin native and mutant peptides. Copyright © 2006 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.744

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractDifferent characteristics of cleavage kinetics of resin‐bound amino alcohols and their peptide derivatives were observed in acid containing protic and aprotic solvent mixtures. The hydrolysis reactions are hindered by steric crowding around the cleaving CO bond and accelerated by the special solvation effect of CF3CH2OH on the peptide chain as well as the increase of the strength and concentration of the acid. In trifluoroacetic acid containing mixtures, trifluoroacetylation of the peptide alcohols was detected. The appearance ofO‐trifluoroacetyl serine and threonine derivatives is detected in cleavage mixtures containing trifluoroacetic acid in anhydrous solvent. Copyright © 2006 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.745

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractThis paper describes the optimization of a synthesis of a difficult sequence related to a 12‐mer sequence of a Pan DR epitope (PADRE). Elongation was followed by on‐line monitoring of theNα‐Fmoc removal adapted for the batch methodology. Studying the intrinsic factors related to the peptide‐resin, such as substitution level, resin nature and backbone protecting group, has led to an increase in the elongation yield and purity of the crude peptide. Optimal elongation was obtained by combining a polar resin such as PEGA and a pseudo‐proline as the backbone protecting group. Copyright © 2006 European Peptide Society and John Wile

ISSN:1075-2617    

DOI:10.1002/psc.746

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY