A New Approach to Glycopeptides

In only three or four steps glycosylated dipeptide and tripeptide fragments, respectively (see scheme), can be obtained from hydroxy amino acids by using a novel protecting group/activation concept. The method presented is even superior to the pentafluorophenyl ester method.     

Caged O-phosphorothioyl amino acids as building blocks for Fmoc-based solid phase peptide synthesis

The synthesis of 1-(2-nitrophenylethyl) caged O-phosphorothioylserine, -threonine, and -tyrosine derivatives is reported. These amino acid building blocks can be directly incorporated into peptides by Fmoc-based solid phase synthesis as their pentafluorophenyl esters or as symmetric anhydrides. Upon irradiation with UV light, the thiophosphate group, representing a hydrolysis resistant phosphate analog, is revealed.     

Synthesis of 2,6-Dimethoxyhydroquinone-3-mercaptoacetyl-peptide-chlorambucil Conjugates

In previous paper, we had reported the synthesis of three conjugates of the cytotoxicity agents: 2,6-Dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA)1, which is a derivative of 2,6-dimethoxy-p-benzoquinone (DMQ). DMQ is a naturally fermented product of wheat germ and was found to have a wide spectrum of cytotoxicity against various tumor cell lines under the synergistic activation of L-ascorbic acid2-5 . Owing to the very low aqueous solubility of DMQ, we prepared derivatives of the …     

Separation of enantiomers on a chiral stationary phase based on ovoglycoprotein: V. Influence of immobilization method on chiral resolution

Ovoglycoprotein from chicken egg whites (OGCHI) was bound to aminopropyl-silica gels via an amino or carboxyl group(s) of OGCHI. In the former case, OGCHI was bound to N,N′-disuccinimidyl carbonate-activated aminopropyl-silica gels, while in the latter case OGCHI activated by a water-soluble carbodiimide and N-hydroxysulfosuccinimide was bound to aminopropyl-silica gels. The obtained OGCHI materials were compared with regard to the bound amounts, retentivity and enantioselectivity. The OGCHI materials prepared via a carboxyl group(s) of OGCHI are suitable for chiral resolution of acidic solutes, and those via an amino group(s) of OGCHI are suitable for chiral resolution of basic solutes. It is suggested that the electrostatic interaction between an amino or carboxyl group of OGCHI and a charged solute should play an important role in chiral recognition of the solute.     

Intermolecular oxygen atom?π interaction in the crystal packing of chiral amino alcohol bearing a pentafluorophenyl group

Presence of an unique atom-to-face alcoholic oxygen atom?π interaction between a pentafluorophenyl group and alcoholic oxygen (O?π) has been demonstrated by X-ray analysis of the novel chiral amino alcohol instead of the well-known interaction between usual aromatic ring and alcoholic hydrogen atom (OH?π).     

The oxazole-triamide rearrangement. Application to peptide synthesis

The carboxyl group of a N-acylated amino acid may be protected by conversion to an oxazole derivative which, on photoxygenation, regenerates the carboxyl group in activated (triamide) form for peptide synthesis.     

Methylating peptides to prevent adduct ion formation also directs cleavage in collision-induced dissociation mass spectrometry

We investigated the effect of N-terminal amino group and carboxyl group methylation on peptide analysis by electrospray mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS). Permethylation of the N-terminal amino group and the carboxyl groups can reduce metal ion adducts but does not enhance sensitivity in electrospray as previously observed for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. N-terminal trimethylated peptides exhibit collision-induced dissociation (CID) tandem mass spectra that differ from their unmodified analogs; the results support the mobile proton hypothesis of peptide fragmentation. A permanent positive charge at the N-terminus leads to competition between permanent-charge directed processes and loss of the N-terminal trimethyl amino group. Carboxyl methylation has no effect on fragmentation behavior other than to shift the mass of fragments containing methylated carboxyl groups. Comparison of regular and tandem mass spectra of different methylated peptides allowed probing the location of incomplete methylation, the proton displaced by alkali metal ions and the purity of a mass-selected methylated peptide ion.     

Chemical structure of polycaproamide obtained by anionic polymerization of caprolactam in solvent

Chemical structure of polycaproamide (nylon-6), obtained by low temperature anionic polymerization of caprolactam in the presence of the sodium salt of caprolactam and carbon dioxide in solvent has been investigated. The polymer formed in a heterogeneous system, depending upon its final treatment, is terminated with amino and cyclic lactam groups or, after hydrolysis, with amino and carboxyl group. i.r. Spectra and acid-base titrations have shown the presence of amino and carboxyl groups in macromolecules. The contents of basic and acidic groups in the final product and its fractions were determined by potentiometric titrations. Number-average molecular weights of samples based on the results of titrations were compared with the results of osmotic measurements. Equal numbers of basic and acid groups in the polymer suggests that macromolecules are terminated at one end by an amino group and at the other by a carboxyl group. The results indicate a linear and regular structure for the polycaproamide.     

An Orthogonally Protected alpha,alpha-bis(aminomethyl)-beta-alanine building block for the construction of glycoconjugates on a solid support

Synthetic glycoclusters are extensively used as mimetics of naturally occurring, multivalent carbohydrate ligands in various glycobiological applications. Their preparation, however, is far from trivial, and it still is a limiting factor in the study of carbohydrate binding. We herein report the synthesis of an orthogonally protected building block, N-Alloc-N'-Boc-N' '-Fmoc-alpha,alpha-bis(aminomethyl)-beta-alanine (1), and its use in the preparation of triantennary peptide glycoclusters (21-24) on a solid support. The assembly of the clusters involves removal of the amino protections of the solid-supported branching unit 1 in the order Fmoc, Boc, and Alloc, and subsequent coupling of peracetylated O-(glycopyranosyl)-N-Fmoc-L-serine pentafluorophenyl esters (galactose, glucose, mannose, and ribose) to each amino group exposed.     

Modeling the reaction mechanisms of the imide formation in an N-(o-carboxybenzoyl)-L-amino acid

Reaction mechanisms of the imide formation in an N-(o-carboxybenzoyl)-l-amino acid have been studied using density functional theory. Our results suggest that the reaction route initiated by protonation at the oxygen of the carboxyl group of the amino acid is favored, while those initiated by deprotonation at the oxygen of the carboxyl group of phthalic acid and at the amidic nitrogen are minor pathways. During the dehydration process, water functions as a catalyst. These conclusions are in good agreement with the experimental facts that at highly acidic conditions (hydrogen ion concentration H(0) < -1), imide formation is the most favorable pathway, whereas in the pH range 0-5, cyclization to the imide is not the dominant reaction. Our calculations also show that the carboxyl group of the amino acid is involved in the catalytic reaction in both the favored and minor pathways and that solvent effects have little influence on the reaction barriers.     

α-氨基酸在水-乙醇中羟基质子化热力学

α 氨基酸为重要的两性物质 ,其酸碱性质对于维持生物体内的酸碱平衡和蛋白质的生物活性起着十分重要的作用．α 氨基酸在纯水溶剂中的质子化反应热力学性质已进行了广泛的研究［１ -６］,但对球形蛋白来说 ,蛋白亚基间的作用是处在一个大量但不完全由水组成的非水环境中 ,因此 ,研究氨基酸在水 有机物混合溶剂中的质子化热力学性质具有重要意义．但这方面的工作 ,特别是用量热法直接研究溶剂对质子化焓变的影响开展得不多．本文选择乙醇和水组成的混合溶剂模拟蛋白质亚基所处的介质环境 ,利用精密微量流动热量计测定２９８．１５Ｋ时甘氨…     

Cyclization of 1-(pentafluorophenyl)-2- aminoalkanols

The nitro group in 1-(pentafluorophenyl)-2-nitroalkanols is reduced selectively to a hydroxylamino or amino group by controlled potential electrochemical reduction. The pentafluoro-phenylaminoalkanols cyclize readily on heating in dimethylformamide to give homologs of 4,5,6,7-tetrafluoroindole. It is shown that the intermediate in the cyclization of 1-pentafluorophenyl-2-aminoethanol is 3-hydroxy-4,5,6,7-tetrafluoroindoline. Cyclization of 1-pentafluorophenyl-2-hydroxyaminoethanol gave 1,3 -dihydroxy-4,5,6,7-tetrafluoroindoline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 622–625, May, 1970.     

α-氨基酸在水-乙醇中羧基质子化热力学

Enthalpy changes for the protonation of carboxyl group of four α-amino acids(glycine,L-α-alanine,L-valine and L-serine) were measured in water-ethanol mixtures (10－ 70wt％) at 298.15K using LKB-2277 Bioactivity Monitor.The corresponding entropy and Gibbs energy changes were also calculated.The results show that both enthalpy changes and entropy changes are favorable to the protonation of carboxyl groups of the investigated amino acids in water-ethanol mixtures.However,the influence of the composition of ethanol in the mixed solvents on the enthalpy change and entropy changes is complicated.Both sδ and sδ ,the differences of enthalpy changes and entropy changes in mixed solvents and in pure water respectively,show a minimum approximately at xEtOH=0.1.The effects of side chains on the enthalpy change and entropy changes were also investigated using the proton transfer process between glycine and the other three amino acids.The results demonstrate that the proton transfer processes for alanine and valine are spontaneous but not for serine,which could be interpreted in terms of the electrostatic interaction between amino group and carboxyl group within the molecule and the interaction between carboxyl group and the solvent.     

Effect of conformational control of chiral oxazaborolidine by π-π stacking interaction of a pentafluorophenyl group toward asymmetric borane reduction

A pentafluorophenyl group can act as a stereo-controlling group in oxazaborolidine-catalyzed asymmetric borane reduction through intramolecular π-π stacking interaction with a phenyl group. The intramolecular π-π interaction in oxazaborolidine bearing pentafluorophenyl group is confirmed by calculations and ¹H NMR study. The interaction affects the enantioselectivity of the asymmetric reduction of acetophenone while the extent is small.     

Synthesis of end‐functionalized AB copolymers. II. Synthesis and characterization of carboxyl‐terminated poly(ethylene glycol)–poly(amino acid) block copolymers

AB block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(amino acid) with a carboxyl group at the end of PEG were synthesized with α‐carboxylic sodium‐ω‐amino‐PEG as a macroinitiator for the ring‐opening polymerization of N‐carboxy anhydride. Characterizations by ¹H NMR, IR, and gel permeation chromatography were carried out to confirm that the diblock copolymers were formed. In aqueous media this copolymer formed self‐associated polymer micelles that have a carboxyl group on the surface. The carboxyl groups located at the outer shell of the polymeric micelle were expected to combine with ligands to target specific cell populations. The diameter of the polymer micelles was in the range of 30–80 nm. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3527–3536, 2004     

Application of DEPBT on the Synthesis of the Protected Dipeptides Containing Histidine with Unprotected Imidazole Group by Solution Method

3- (Diethoxyphosphoryloxy)- 1,2,3-benzotriazln-4 (3H)-one (DE-PBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing Tyr, Ser and Thr with unprotected hydroxy group on their side chain. The further study of the synthesis of a series of protected dipeptides containing hisfidine with unprotected imidazole group using DEPBT is reported. During the synthetic procedure, the imidazole group of histidine did not need to be protected. When the carboxyl components were N-protected aromatic amino acids or basic amino acids, the yields were relatively high (63%--81%). However,when the carboxyl components were N-protected acidic amino acids, the yields were relatively low (47%--48%). The results expanded the application of DEPBT on the synthesis of bioactive peptides containing histidine.     

NMR Studies of a New Binding Mode of the Amino Acid Esters by Porphyrinatozinc(Ⅱ)

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Quantitative analysis of a proteome by N-terminal stable-isotope labelling of tryptic peptides

Covalent modification of peptides and proteins with compounds containing stable isotopes (isotope tagging) has become an essential tool to detect dynamic changes in the proteome following external or internal influence; however, using terminal amino groups for global isotope labelling of tryptic peptides is challenged by the similar reactivity of the amino groups of lysine residues. We describe a new quantitative method based on selective tagging of the terminal amino groups of tryptic peptides with pentafluorophenyl esters containing stable isotopes. The labelled peptides were resolved by two-dimensional nanoflow liquid chromatography on weak anion-exchange and reversed-phase columns and then identified and quantified by tandem mass spectrometry. The method was applied to compare the proteomes of plasma membranes from proliferating and differentiated human colorectal adenocarcinoma (Caco-2) cells and endosomes purified from the livers of rats stimulated with insulin and epidermal growth factor. The comparison of the results obtained by isotope tagging and biochemical assays demonstrate that global isotope tagging with pentafluorophenyl esters allows accurate quantification of complex protein samples.     

A simple and efficient synthesis of functionalized cyclic carbonate monomers using a versatile pentafluorophenyl ester intermediate

An improved two-step synthetic route to functionalized cyclic carbonate monomers that features a novel cyclic carbonate intermediate with an active pentafluorophenyl ester group (MTC-OPhF(5)) has been developed. The versatile pentafluorophenyl ester intermediate can be synthesized on the gram to kilogram scale in one high-yielding step and is easy to store and handle on the benchtop. The active pentafluorophenyl ester of MTC-OPhF(5) is amenable to further substitution with suitable nucleophiles such as alcohols and amines to generate functionalized cyclic carbonates in high yields. The substitution reaction is tolerant of a wide variety of functionalities, including various hydrophobic and hydrophilic groups, reactive functionalities (via thiol-ene click chemistry or alkyl halides), and protected acids, alcohols, thiols, and amines. In view of the ever-increasing need for biodegradable and biocompatible polymers, this new methodology provides a simple and versatile platform for the synthesis of new and innovative materials.     

ENERGETICS OF PROTONATION-DEPROTONATION OF THE CHROMOPHORE IN RETINAL PROTEINS

Abstract— We investigate the energetics of protonation and deprotonation of retinylidene Schiff-base (SB) which is realized in the functioning of retinal proteins. We first calculate the energy difference ΔE between the protonated and unprotonated states of the SB by the ab initio molecular orbital method, using two kinds of molecular model; a counter-ion model where a carboxyl group of Glu or Asp is directly hydrogen-bonded to the SB, and a water-bridge model where a water molecule bridges the carboxyl group and the SB. The calculated results indicate that the protonated SB state is unstable compared with the unprotonated SB state in either model. In addition, we find that coordination of some water molecules to the carboxyl group reduces ΔE significantly. The value of AE for the counterion model with two coordinated water molecules is 0.003 eV. Next, we calculate the electrostatic interaction energy between a tryptophan residue and the SB. We find that the protonated state is more stabilized than the unprotonated state by about 0.1 eV with one tryptophan residue. This fact indicates that if some aromatic amino acid residues work cooperatively, they can contribute to significantly reducing ΔE. We also discuss the possible role of amino acid residues which make hydrogen-bond with the carboxyl group of interest.