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1.
A new method for the preparation of peptide thioester by the post-solid phase peptide synthesis (SPPS) approach was developed. A series of N-alkyl cysteine derivatives were prepared and used as the C-terminus residue of the peptides prepared by the Fmoc SPPS. The synthetic peptides released from resin by TFA were readily converted to the peptide thioester in aqueous 3-mercaptopropionic acid (MPA) without significant side reactions.  相似文献   

2.
We describe here a novel and convenient synthesis of head-to-tail cyclic peptide avoiding racemization. Linear depsipeptides including a serine residue as the key element for ester bond formation and acyl transfer were synthesized on 2-chlorotrityl chloride resin. After cleavage from the resin, intramolecular head-to-tail cyclization was performed in solution by C-terminal activation of urethane protected O-acyl serine residue. After removal of the Nα-serine protecting group, the final step consisted in O-N-acyl migration reaction on the ‘switch’ or ‘click’ element to restore native cyclic peptides.  相似文献   

3.
A novel strategy of solid phase synthesis of N-cycloguanidinyl-formyl peptides has been established and investigated which involved coupling orthogonal protected diaminoacid with resin bound peptide, α-amino group deprotection, guanidinylation of α-amino group by bis-Cbz-1H-pyrazole-1-carboxamidine followed by cleavage and cyclization in solution, and finally removing Cbz by palladium catalyzed hydrogenation. Through this method, cycloguanidine could be introduced to either N-terminus or sidechain of designated peptides. The reaction conditions were facile, straightforward, and totally adaptive to common solid phase peptide synthesis strategy.  相似文献   

4.
Mass Spectrometry (MS) analysis of pyrolysis products of simple peptides has revealed several non-volatile thermal degradation products at masses lower than the precursor peptide. In addition to these products, many other signals were also observed at higher masses than the precursor peptide, and their characterization is the focus of this study. Here we report on the observation of homo and hetero condensation peptide products formed during the pyrolysis of peptides. The observed peptide condensation products are formed between two, three or even four peptides. Tandem MS (MS/MS) analyses of these products showed that C-terminal to N-terminal intermolecular bonding is preferred during pyrolysis when combining two peptides, rather than involving crosslinking between basic and acidic side chain groups like arginine and aspartic acid. These observations are rationalized by steric hindrance effect and known pKa values of the peptide C- and N-termini and amino acid side groups like aspartic acid and arginine. Pyrolysis of a standard N-acetylated peptide showed no detectable condensation and/or crosslinked products, even in peptides with basic side groups, providing further evidence for the C-terminus to N-terminus intermolecular bonding between peptides under pyrolytic conditions.  相似文献   

5.
《中国化学快报》2020,31(5):1162-1164
Herein, we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled by β-cyclodextrin (β-CD) based host-guest recognitions. This nanovaccine can generate significant titers of antibodies and improve the therapeutic effect against melanoma, suggesting the immunogenicity of peptide antigens can be improved by loading with this carrier. The novel vaccine carrier provides a platform for the transport of various antigens especially T cell-independent antigens.  相似文献   

6.
The Goldschmidt-Wick type reaction between isocyanates of Nα-Fmoc-amino acids/peptide acids and Nα-Boc-/Z-/Bsmoc-amino acids catalyzed by DMAP leads to the incorporation of a reversed peptide bond. It was found to be a simple, efficient and clean reaction. All the retro-inverso peptides made were obtained as crystalline compounds in 70-92% yields.  相似文献   

7.
A novel ‘O-acyl isodipeptide unit’, Boc-Thr(Fmoc-Val)-OH 5 has been successfully used for the efficient synthesis of a difficult sequence-containing pentapeptide based on the ‘O-acyl isopeptide method’, in which racemization-inducible esterification could be omitted, suggesting that the use of O-acyl isodipeptide units allows the application of this method to fully automated protocols for the synthesis of long peptides or proteins.  相似文献   

8.
A novel and convenient method for the synthesis of C-terminally branched collagen-model peptides has been achieved using tricine (N-[tris(hydroxymethyl)methyl]glycine) as a branching scaffold and 1,2-diaminoethane or 1,4-diaminobutane as a linker. The peptide sequence was incorporated directly onto the linker and scaffold during solid-phase synthesis without additional manipulations. The resulting branched triple-helical peptides exhibited comparable thermal stabilities to the parent, unbranched sequence, and served as substrates for matrix metalloproteinase-1 (MMP-1). The tricine-based branch reported herein represents the simplest synthetic scaffold for the convenient synthesis of covalently linked homomeric collagen-model triple-helical peptides.  相似文献   

9.
Biological membrane fusion is a highly specific and coordinated process as a multitude of vesicular fusion events proceed simultaneously in a complex environment with minimal off-target delivery. In this study, we develop a liposomal fusion model system with specific recognition using lipidated derivatives of a set of four de novo designed heterodimeric coiled coil (CC) peptide pairs. Content mixing was only obtained between liposomes functionalized with complementary peptides, demonstrating both fusogenic activity of CC peptides and the specificity of this model system. The diverse peptide fusogens revealed important relationships between the fusogenic efficacy and the peptide characteristics. The fusion efficiency increased from 20% to 70% as affinity between complementary peptides decreased, (from KF ≈ 108 to 104 M−1), and fusion efficiency also increased due to more pronounced asymmetric role-playing of membrane interacting ‘K’ peptides and homodimer-forming ‘E’ peptides. Furthermore, a new and highly fusogenic CC pair (E3/P1K) was discovered, providing an orthogonal peptide triad with the fusogenic CC pairs P2E/P2K and P3E/P3K. This E3/P1k pair was revealed, via molecular dynamics simulations, to have a shifted heptad repeat that can accommodate mismatched asparagine residues. These results will have broad implications not only for the fundamental understanding of CC design and how asparagine residues can be accommodated within the hydrophobic core, but also for drug delivery systems by revealing the necessary interplay of efficient peptide fusogens and enabling the targeted delivery of different carrier vesicles at various peptide-functionalized locations.

We developed a liposomal fusion model system with specific recognition using a set of heterodimeric coiled coil peptide pairs. This study unravels important structure–fusogenic efficacy relationships of peptide fusogens.  相似文献   

10.
A novel fluorescence (FL) reaction for N-terminal Gly-containing peptides has been developed using 3,4-dihydroxyphenylacetic acid (3,4-DHPAA). The reaction of the peptides with 3,4-DHPAA was carried out in borate buffer (pH 8.0) in the presence of sodium periodate at 37 °C for 10 min, and the FL was measured with a spectrofluorimeter at the excitation and emission wavelengths of 370 nm and 465 nm, respectively. The 3,4-DHPAA reagent generated particularly strong FL for peptides containing Gly at their N-termini. When various other bio-substances, such as amino acids, sugars, nucleic bases, nucleotides, and proteins, were reacted with 3,4-DHPAA, no FL was observed. Under optimized reaction conditions, the lower detection limit of 0.25 μmol L−1 was obtained for the N-terminal Gly-containing peptides of Gly-Pro (GP) and Gly-Pro-Pro (GPP), which gave 3 times greater FL intensity than that observed for the reagent blank. The proposed reaction with 3,4-DHPAA as a fluorogenic reagent is selective and sensitive for the detection of N-terminal Gly-containing peptides, and therefore, this method could be a useful tool for the determination of these particular oligopeptides.  相似文献   

11.
The ComX pheromone is a post-translationally modified oligopeptide that stimulates natural genetic competence controlled by quorum sensing in Bacillus subtilis. Recently, the structure of the ComXRO-E-2 pheromone produced by strain RO-E-2 was determined. Based on the NMR analysis, a geranyl group is bound to the tryptophan residue, which results in the formation of a tricyclic ring structure. It was proposed that one of the four possible stereochemical isomers was based on a conformational search for model compounds and the assumption that amino acid residues in the natural pheromone have the l-configuration. All possible modified tryptophan residues and the corresponding ComXRO-E-2 peptides were synthesized to confirm the precise stereochemistry. Here, the synthesis of the modified tryptophan derivatives was reported in detail. It was succeeded in synthesizing four optically active modified tryptophan methyl esters from which the four diastereomeric ComXRO-E-2 peptides were prepared. Since only one of the four diastereomers was spectroscopically identical to the natural pheromone and exhibited biological activity, the absolute structure of the ComXRO-E-2 pheromone was able to be established unambiguously. Furthermore, it was noticed that two other bioactive pheromones were present in the culture broth that were co-purified with ComXRO-E-2 pheromone. These pheromones were presumed to be the N-terminal truncated peptides of ComXRO-E-2 pheromone, i.e., [2-6]ComXRO-E-2 and [3-6]ComXRO-E-2, by LC-MS and NMR analyses. Using Fmoc solid-phase peptide synthesis, ComXRO-E-2 pheromone and the [2-6]ComXRO-E-2 and [3-6]ComXRO-E-2 peptides were prepared. The synthetic peptides were identical to the natural pheromones and also showed significant biological activity.  相似文献   

12.
To quantify a therapeutic PEGylated protein in monkey serum as well as to monitor its potential in vivo instability and methionine oxidation, a novel ultra high performance liquid chromatography-high resolution mass spectrometric (UHPLC-HRMS) assay was developed using a surrogate disulfide-containing peptide, DCP(SS), and a confirmatory peptide, CP, a disulfide-free peptide. DCP(SS) was obtained by eliminating the step of reduction/alkylation before trypsin digestion. It contains an intact disulfide linkage between two peptide sequences that are essential for drug function but susceptible to potential in vivo cleavages. HRMS-based single ion monitoring (SIM) on a Q Exactive™ mass spectrometer was employed to improve assay specificity and sensitivity for DCP(SS) due to its poor fragmentation and low sensitivity with SRM detection. The assay has been validated for the protein drug in monkey serum using both surrogate peptides with excellent accuracy (within ±4.4%Dev) and precision (within 7.5%CV) with a lower limit of quantitation (LLOQ) at 10 ng mL−1. The protein concentrations in monkey serum obtained from the DCP(SS)-based assay not only provided important pharmacokinetic parameters, but also confirmed in vivo stability of the peptide regions of interest by comparing drug concentrations with those obtained from the CP-based assay or from a ligand-binding assay (LBA). Furthermore, UHPLC-HRMS allowed simultaneous monitoring of the oxidized forms of both surrogate peptides to evaluate potential ex vivo/in vivo oxidation of one methionine present in each of both surrogate peptides. To the best of our knowledge, this is the first report of using a surrogate disulfide-containing peptide for LC-MS bioanalysis of a therapeutic protein.  相似文献   

13.
Simon Stamm 《Tetrahedron》2006,62(41):9671-9680
A method for the direct introduction of Aib-Pro into peptides on solid phase was developed. The Aib-Pro unit was introduced by means of the ‘azirine/oxazolone method’ using allyl N-(2,2-dimethyl-2H-azirin-3-yl)-l-prolinate as the synthon. After the reaction of the resin-bound amino or peptide acid with allyl N-(2,2-dimethyl-2H-azirin-3-yl)-l-prolinate, the allyl protecting group of the resulting extended peptide could be removed by a mild Pd0-promoted procedure. Cleavage of the peptide from the resin was performed with UV light at 352 nm and yielded C-terminal protected peptides. The method found a successful application in the syntheses of different Aib-Pro containing peptaibol segments. Furthermore, a protected derivative of the peptide antibiotic Trichovirin I 1B was prepared by segment condensation.  相似文献   

14.
The 1,5-disubstituted tetrazole ring a mimetic of the cis-amide bond is an unique element modifying the ability of peptides to chelate copper(II) ions. The position of the tetrazole ring system in the peptide backbone plays a critical role in the stabilization of the metallopeptide molecule. The insertion of a tetrazole between amide groups leads to enhancing the stability of the complex and to obtaining a very effective peptide chelating agent. These findings can provide important information for modeling biologically relevant peptide–metal binding sites. Some aspects of biological activity of tetrazole modified exogenous opioid peptides in the presence of copper(II) ions are also presented in this review.  相似文献   

15.
The first application of a combination of novel ψ[(E)-CXCX]-type alkene dipeptide isosteres to conformation studies of cyclic bioactive peptides was carried out (X=H or Me). For exploration of bioactive conformations of Kessler's cyclic RGD peptides, cyclo(-Arg-Gly-Asp-d-Phe-Val-) 1 and cyclo(-Arg-Gly-Asp-d-Phe-N-MeVal-) 2, d-Phe-ψ[(E)-CXCX]-l-Val-type dipeptide isosteres were utilized having di-, tri- and tetrasubstituted alkenes containing the γ-methylated isosteres that have been reported to be potential type II′ β-turn promoters. All of the (E)-alkene pseudopeptides 3-6 exhibited higher antagonistic potency against αvβ3 integrin than 1, although potencies were slightly lower than 2. Detailed structural analysis using 1H NMR spectroscopy revealed that representative type II′ β/γ backbone arrangements proposed for 1, were not observed in peptides 3-6. Rather on the basis of 1H NMR data, the conformations of peptides 3-6 were estimated to be more analogous to those of the N-methylated peptide 2.  相似文献   

16.
Membrane binding of proteins such as short chain dehydrogenase reductases or tail-anchored proteins relies on their N- and/or C-terminal hydrophobic transmembrane segment. In this review, we propose guidelines to characterize such hydrophobic peptide segments using spectroscopic and biophysical measurements. The secondary structure content of the C-terminal peptides of retinol dehydrogenase 8, RGS9-1 anchor protein, lecithin retinol acyl transferase, and of the N-terminal peptide of retinol dehydrogenase 11 has been deduced by prediction tools from their primary sequence as well as by using infrared or circular dichroism analyses. Depending on the solvent and the solubilization method, significant structural differences were observed, often involving α-helices. The helical structure of these peptides was found to be consistent with their presumed membrane binding. Langmuir monolayers have been used as membrane models to study lipid–peptide interactions. The values of maximum insertion pressure obtained for all peptides using a monolayer of 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE) are larger than the estimated lateral pressure of membranes, thus suggesting that they bind membranes. Polarization modulation infrared reflection absorption spectroscopy has been used to determine the structure and orientation of these peptides in the absence and in the presence of a DOPE monolayer. This lipid induced an increase or a decrease in the organization of the peptide secondary structure. Further measurements are necessary using other lipids to better understand the membrane interactions of these peptides.  相似文献   

17.
《Supramolecular Science》1997,4(3-4):365-368
Synthetic peptides constructed with doublets of hydrophobic residues tandemly repeated with doublets of positively charged residues, (Leu-Lys-Lys-Leu)n, were used as models for the study of protein-membrane interactions. Their behaviour has been compared with that of their strictly alternating iso peptides, (Leu-Lys)n. Both peptides present a random coil structure in pure water. In saline solutions, (Leu-Lys-Lys-Leu)n peptides adopt an α-helical structure whereas (Leu-Lys)n transit into a β-sheet structure. These peptides form multilayer assemblies on a pure water subphase but they are organized in monomolecular films on a saline aqueous subphase. The stability of these films increases with the peptide length. Structured peptides (α helices and β sheets) penetrate readily into lipid monolayers, whereas the penetration of unordered peptides is very slow. We have not observed any significant difference between the behaviour of a helices and β-sheet structures.  相似文献   

18.
A synthetic strategy to prepare o-NBS protected Fmoc-amino acids under mild conditions, in a rapid and efficient way, characterised by high yields and excellent purity of the final products has been developed. The o-NBS protected Fmoc-amino acids are employed in solid phase peptide synthesis to prepare peptidomimetics carrying mono-benzylated moieties on peptide side chains.  相似文献   

19.
A fluorimetric method is proposed for determining N-terminal tyrosine-containing peptides, of which some peptides such as enkephalins and kyotorphin are of physiological importance. An intense fluorescence is produced when the peptide is heated at 100°C for 3 min in a weakly alkaline medium containing borate, hydroxylamine and cobalt(II). The fluorescent species is stabilized with β-mercaptoethanol, with excitation and emission maxima at 335 and 430 nm, respectively. The method is highly selective for N-terminal tyrosine-containing peptides, with a detection limit of 43–69 pmol ml?1.  相似文献   

20.
Antonella Leggio 《Tetrahedron》2007,63(34):8164-8173
A highly efficient and practical synthesis of peptides in solution phase has been developed. The procedure is based on the use of p-nitrobenzenesulfonyl (nosyl) group for the protection of the amino function of α-amino acids. Every step of the procedure, protection of the amino function by the nosyl group, formation of the peptide bond, and removal of the sulfonamide group, is characterized by high yields and excellent purity of the final products. The described strategy allows the preparation of short peptide sequences keeping the chiral integrity of amino acid precursors. Compatibility of nosyl group with the side-chain protecting groups used in Fmoc-based strategy is demonstrated. The method here presented is an alternative strategy that could provide advantages for future peptide synthesis.  相似文献   

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