Synthesis of Chiral Tetrahomodiazacalix[4]-and [6]Arenes Bridged by Cystine Peptide

Bicyclic tetrahomodiazacalix[4]- and [6]arenes bridged by a cystine peptide were easily synthesized from the cyclization reactions of bis(chloromethyl)phenol-formaldehyde oligomers with cystine peptides in DMF in moderate yields.     

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric observation of a peptide triplet induced by thermal cleavage of cystine.

Heat-induced (90 degrees C, 30 min) beta-elimination of a cystine residue leads to cleavage of a disulfide bond and produces a set of three peptides with a cysteine residue, a thiocysteine residue (+32Da), and a dehydroalanine residue (-34Da). This characteristic feature was observed from somatostatin and insulin by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Mass spectrometric observation of this triplet is useful in identifying the presence of a cystine residue in a peptide, and could assist mass spectrometric identification of the peptide from a database.     

Determination of the amino acid sequence of cystine-containing peptides by tandem mass spectrometry.

A method has been developed for the determination of the amino-acid sequence of a cyclic peptide containing cystine. It is based on the reduction of the peptide in a reductive matrix prior to ionization by fast-atom bombardment. The amino-acid sequence of the resulting linear peptide is then determined by tandem mass spectrometry from the spectrum produced by the collision-induced decomposition of the [M + H]+ ion of the peptide.     

Novel observation of a circular dichroism band originating from amyloid fibril.

A peptide fragment of a non-amyloid-beta component (NAC(1-13)) was studied by CD and electron microscopy. Typical amyloid fibrils were observed by EM in a solution of NAC(1-13). In addition to the beta-structural CD band in the far-UV region, a novel CD band near 285 nm was observed in a peptide solution of NAC(1-13). Taking the NAC(1-13) to contain neither an aromatic amino acid residue nor cystine into account, the CD band can be attributed to amyloid fibrils of NAC(1-13).     

几种酚醛树脂热裂解的研究

采用热失重、差热分析、热机分析、裂解气体容积分析及组分的色谱分析等方法,对几种热固性酚醛树脂的热裂解进行了研究。结果表明酚醛树脂的热稳定性与二亚甲基醚键的存在很有关系,随着醚键的增多而热稳定性降低。对树脂的热裂解机理进行了讨论。     

Diaminodiacid Bridges to Improve Folding and Tune the Bioactivity of Disulfide‐Rich Peptides

Disulfide‐rich peptides containing three or more disulfide bonds are promising therapeutic and diagnostic agents, but their preparation is often limited by the tedious and low‐yielding folding process. We found that a single cystine‐to‐diaminodiacid replacement could significantly increase the folding efficiency of disulfide‐rich peptides and thus improve their production yields. The practicality of this strategy was demonstrated by the synthesis and folding of derivatives of the μ‐conotoxin SIIIA, the preclinical hormone hepcidin, and the trypsin inhibitor EETI‐II. NMR and X‐ray crystallography studies confirmed that these derivatives of disulfide‐rich peptide retained the correct three‐dimensional conformations. Moreover, the cystine‐to‐diaminodiacid replacement enabled structural tuning, thereby leading to an EETI‐II derivative with higher bioactivity than the native peptide.     

STM vizualization of thiol-containing peptide dendrimers on Au(111)

Peptide dendrimers assembled by solid-phase peptide synthesis using a branching diamino acid at every 2(nd) or 3(rd) position provide readily accessible synthetic model systems for proteins and enzymes. They adopt a globular shape by topology rather than by folding. Peptide dendrimers of 2(nd) and 3(rd) generation functionalized with a cysteine or cystine residue in the core were adsorbed on Au(111) surface and imaged by STM at air, under UHV, or in solution. The dendrimers appear as globular features with dimensions suggesting an extended flattened conformation, forming both single globules and ordered arrays on the surface. These images represent the first direct visualization of peptide dendrimer enzyme models.     

The Structure of Some Phenol-Formaldehyde Condensates for Wood Adhesives

The probable minimum-energy structures of three dimeric, three tri-meric, and two hexameric phenol-formaldehyde (PF) condensates were determined by using a simplified model where the total energy was calculated as the sum of the van der Waals, hydrogen bonding, torsional, and electrostatic energies. The minimum-energy conformation was defined as that with internal angles of rotation that correspond to the overall minimum in the total energy. Representations of the structures of these PF condensates in the minimum-energy conformations were obtained. The results obtained indicated that the van der Waals energy, and in some cases the hydrogen bonding energy, make the most important contributions to the total energy. The phenol-formaldehyde dimers and trimers are predicted by this model to have nonplanar structures, and the longer phenol-formaldehyde condensates, such as the hexamers, probably exist in helical conformations.     

Adhesives and coatings from phenol-formaldehyde/resorcinol-formaldehyde resins

Resole phenol-formaldehyde resins were prepared and modified with the prepared resorcinol-formaldehyde resins. The optimum conditions of formulation and curing processes were studied to obtain modified wood adhesives characterized by high-tensile shear strength values. This study indicated that the more suitable conditions are equal weight ratios of phenol-formaldehyde to resorcinol-formaldehyde resins in the presence of paraformaldehyde (10 or 15 wt%) of the resin content as a curing agent at 80 or 25°C for 40 min or 100–110 days, respectively. The activation energies of the curing reactions for phenol-formaldehyde/resorcinol-formaldehyde resin samples were determined. Metallic and glass coatings from the previous pure resins and their formulated cured mixtures were prepared and evaluated as varnishes or paints. Copyright © 1998 John Wiley & Sons, Ltd.     

The effect of environment on cystine disruption by ultraviolet light

When cystine is irradiated at pH 1 by 254-nm u.v. the following yields are observed: 4 cystines → 5.2 cysteines + 2.8NH₃. Thus, SH production accounts for only 0.65 of the cystine destruction; further C-S breakage to give alanine or serine is not efficient. The yields for cystine and glutathione destruction are essentially the same at pH 1. However the presence of the glutamic and glycine residues stabilize the cystine in glutathione so that NH₃ is not lost until the peptide bonds are hydrolyzed. Increasing the pH from 1 to 8.6 increases the yield of cystine destruction in glutathione by 50 per cent. The yield of cystine destruction is greater in both compounds when O₂ is present during irradiation (e. g. the cysteic acid yield in glutathione is increased by 50 times). The overall production of SH varies by a factor of 2 in the four proteins-insulin, RNase, trypsin and lysozyme. The present data further support the earlier observation that radiation damage is quite non-random in RNase: at least two and perhaps three of the four constituent cystines must be disrupted before activity is lost: i.e. the most radiosensitive cystines are not critical for enzymic activity. Similarly, in both trypsin and lysozyme the integrity of the most radiosensitive cystines also does not appear to be critical for the retention of enzymic potential. In insulin, however, all three cystines appear to be crucial for activity and to have approximately equal radiosensitivities. These differences in sensitivity of cystines in different proteins must depend specifically upon energy transfer and/or chemical interactions between the chromophoric groups. If yields are calculated on the basis of those quanta absorbed only in the cystines, values about 5 to 8 times greater than those in the model compounds cystine and oxixized glutathione are obtained. The yields of cystine destruction are much higher in those protiens which contain trypotophan.     

The Synthesis of Cystine Peptides by Iodine Oxidation of S-Trityl-cysteine and S-Acetamidomethyl-cysteine Peptides

Previously reported studies of the iodine oxidation of S-trityl-cysteine peptides and S-acetamidomethyl-cysteine peptides, leading directly to cystine peptides, have been extended. Detailed investigations have been made of the reactivities of the S-trityl and the S-acetamidomethyl group towards iodine in various solvents. In chloroform, methylene chloride, trifluoroethanol, and hexafluoroisopropyl alcohol the differences in the reaction rates of the two groups have been found to be extremely large, allowing the selective conversion of the tritylthio groups to disulfides in the presence of the S-acetamidomethyl derivatives. In a second group of solvents, consisting of methanol, acetic acid, dioxane, and mixtures of these solvents with water, simultaneous iodine oxidation of S-trityl- and S-acetamidomethyl-cysteine peptides leads to a preferential combination of these two residues, resulting in predominantly asymmetrical cystine derivatives. - The suitability of the two sulfur-protecting groups in the synthesis of cyclic cystine peptides has been assessed. - Possible reaction mechanisms are discussed. - The scope and limitations of iodine oxidation in peptide synthesis have been studied. The applicability of the method has been demonstrated in the preparation of the open-chain asymmetrical cystine peptide 5 , the protected somatostatin derivative 17 , and the A(1–13) segment 19 of human insulin, previously employed in the total synthesis of this hormone.     

Asteropine A, a sialidase-inhibiting conotoxin-like peptide from the marine sponge Asteropus simplex

Marine sponges contain structurally intriguing and biologically active peptides of nonribosomal peptide synthase origin, often containing amino acids with novel structures. Here we report the discovery of asteropine A (APA), a cystine knot to be isolated from marine sponges. The solution structure of APA as determined by NMR belongs to the four-loop class of cystine knots similar to those of some conotoxins and spider toxins. However, the highly negatively charged surface of APA is uncommon among other cystine knots. APA competitively inhibits bacterial sialidases, but not a viral sialidase. APA was inactive against all other enzymes tested and did not have any apparent antitumor activity. Our data suggest that APA and other knotting peptides may be important leads for antibacterial and even antiviral drug development.     

Syntheses of chiral homoazacalix[4]arenes incorporating amino acid residues: molecular recognition for racemic quaternary ammonium ions

Chiral calixarene analogues incorporating amino acid residues into the macrocyclic rings were prepared from the cyclization reactions of bis(chloromethyl)phenol-formaldehyde tetramer with amino acid methyl ester in moderate yields. The macrocycles form a chiral concavity, which is induced by the chiral transmission from the point chirality of the amino acid residues to the phenol-formaldehyde tetramer unit. The macrocycles have the cavity pi-basic enough to include the quaternary ammonium ion due to the cation-pi interaction and can serve as a shift reagent for racemic ammonium ions during 1H NMR analysis.     

Designer peptide dendrimers using click reaction

We designed and synthesized various peptide dendrimers using a 1,3-dipolar cycloaddition (Click) reaction. The dendritic structures reported here include symmetrical, asymmetrical, and cationic dendrimers with triazole, cystine, aromatic, aliphatic, and Lys-Asp dipeptide cores. The high chemoselectivity of the click reaction allowed us to synthesize good yields of high-purity protected and unprotected dendritic structures. Triazole is an excellent peptide bond mimic, which remains hydrolytically stable. Dendrimer 15a and the core unit 21 gelate in a mixture of organic solvents. We also demonstrated the versatility of the design by synthesizing various carbohydrate-based dendrimers.     

A novel approach to the regioselective synthesis of a disulfide-linked heterodimeric bicyclic peptide mimetic of brain-derived neurotrophic factor

We describe a novel acetamidomethyl to S-pyridinyl exchange that is used for the synthesis of a multi-disulfide-linked and constrained heterodimeric bicyclic peptide mimetic of brain-derived neurotrophic factor (BDNF). This simple and effective method should be readily transferable to the synthesis of similar disulfide-linked heterodimeric peptides, as well as being of general utility for the synthesis of peptides bearing multiple cystine frameworks.     

Facile Syntheses of Homothiacalixarenes

Homothiacalixarenes were conveniently prepared from the reactions of bis(chloromethyl)phenol-formaldehyde trimers with alkanedithiols in good yields.     

Electrochemical behavior and voltammetric determination of cysteine and cystine at carbon-paste electrodes modified with metal phthalocyanines

The electrochemical behavior of cysteine and cystine on carbon-paste electrodes modified with Fe(II), Co(II), Ni(II), and Cu(II) phthalocyanines is studied. Metal phthalocyanines exhibit catalytic activity in the electrooxidation of cysteine and cystine and in the reduction of cystine. The best catalyst is the cobalt complex. In the electrooxidation of cysteine, the catalysts are electrogenerated complex species of Co(II)Pc or Co(III)Pc⁺, and in the oxidation of cystine, oxidized or reduced forms of the coordinated ligand. Various versions of the determination of cysteine and cystine by the electrocatalytic reactions on the modified electrodes are proposed.     

人参寡肽的合成

使用溶液和有机磷肽缩合试剂DEPBT合成了从人参中分离鉴定的三个寡肽,N,N'－双－(γ-谷氨酰甘氨酰)胱氨酸1,N,N'－双-γ－谷氨酰胱氨酰甘氨酸2,N-γ-谷氨酰胱氨酰-双-甘氨酸3,以及γ-谷氨酰甘氨酰半胱氨酸。4.产物经离子交换树脂柱或HPLC纯化,用质谱、核磁共振谱、氨基酸分析进行了验证。     

双烟酰基取代的类环肽合成及对二价铜离子的配位研究

在模拟蛋白质的分子识别功能方面,人工合成以氨基酸为主要结构单元的环肽由于更接近于生命物质,因此作为主体分子来模拟生命现象更贴切.目前,这方面的研究主要集中在环肽对碱金属、碱土金属以及磷酸酯的识别或跨膜传输等方面.环肽通过骨架或侧臂与过渡金属离子的配位研究也仅有几例.实际上,许多过渡金属,如Cu(Ⅱ),Zn(Ⅱ)和Fe(Ⅱ)等在稳定蛋白质的构象及增强.     

Analyse der monomeren Komponenten in Phenol-Formaldehyd-Kondensaten

Zusammenfassung Zwischen den durch Titration und den aus Gel-Chromatogrammen bestimmten Gehalten an freiem Phenol in Kondensaten aus Phenol und Formaldehyd bestehen Unterschiede. Ursache dafür ist ein Anteil an methylolgruppenhaltigen monomeren Harzkomponenten.

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Analysis of monomeric components in phenol-formaldehyde condensates

Summary There is a difference in the content of free phenol in phenol-formaldehyde resins determined by titration and calculated from GPC. This is caused by methylolgroup containing monomeric components in the resins.

Wir danken der Arbeitsgemeinschaft Industrieller Forschungsvereinigungen (AIF) für die Förderung dieser Untersuchungen.