排序方式: 共有17条查询结果,搜索用时 15 毫秒
1.
Iris A. Bermejo Claudio D. Navo Jorge Castro-Lpez Ana Guerreiro Ester Jimnez-Moreno Elena M. Snchez Fernndez Fayna García-Martín Hiroshi Hinou Shin-Ichiro Nishimura Jos M. García Fernndez Carmen Ortiz Mellet Alberto Avenoza Jesús H. Busto Gonalo J. L. Bernardes Ramn Hurtado-Guerrero Jesús M. Peregrina Francisco Corzana 《Chemical science》2020,11(15):3996
The Tn antigen (GalNAc-α-1-O-Thr/Ser) is a well-known tumor-associated carbohydrate determinant. The use of glycopeptides that incorporate this structure has become a significant and promising niche of research owing to their potential use as anticancer vaccines. Herein, the conformational preferences of a glycopeptide with an unnatural Tn antigen, characterized by a threonine decorated with an sp2-iminosugar-type α-GalNAc mimic, have been studied both in solution, by combining NMR spectroscopy and molecular dynamics simulations, and in the solid state bound to an anti-mucin-1 (MUC1) antibody, by X-ray crystallography. The Tn surrogate can mimic the main conformer sampled by the natural antigen in solution and exhibits high affinity towards anti-MUC1 antibodies. Encouraged by these data, a cancer vaccine candidate based on this unnatural glycopeptide and conjugated to the carrier protein Keyhole Limpet Hemocyanin (KLH) has been prepared and tested in mice. Significantly, the experiments in vivo have proved that this vaccine elicits higher levels of specific anti-MUC1 IgG antibodies than the analog that bears the natural Tn antigen and that the elicited antibodies recognize human breast cancer cells with high selectivity. Altogether, we compile evidence to confirm that the presentation of the antigen, both in solution and in the bound state, plays a critical role in the efficacy of the designed cancer vaccines. Moreover, the outcomes derived from this vaccine prove that there is room for exploring further adjustments at the carbohydrate level that could contribute to designing more efficient cancer vaccines.An anti-cancer vaccine based on an unnatural antigen with an sp2-iminosugar fragment. 相似文献
2.
Hajime Wakui Yoshikazu Tanaka Toyoyuki Ose Isamu Matsumoto Koji Kato Yao Min Taro Tachibana Masaharu Sato Kentaro Naruchi Fayna Garcia Martin Hiroshi Hinou Shin-Ichiro Nishimura 《Chemical science》2020,11(19):4999
Aberrantly truncated immature O-glycosylation in proteins occurs in essentially all types of epithelial cancer cells, which was demonstrated to be a common feature of most adenocarcinomas and strongly associated with cancer proliferation and metastasis. Although extensive efforts have been made toward the development of anticancer antibodies targeting MUC1, one of the most studied mucins having cancer-relevant immature O-glycans, no anti-MUC1 antibody recognises carbohydrates and the proximal MUC1 peptide region, concurrently. Here we present a general strategy that allows for the creation of antibodies interacting specifically with glycopeptidic neoepitopes by using homogeneous synthetic MUC1 glycopeptides designed for the streamlined process of immunization, antibody screening, three-dimensional structure analysis, epitope mapping and biochemical analysis. The X-ray crystal structure of the anti-MUC1 monoclonal antibody SN-101 complexed with the antigenic glycopeptide provides for the first time evidence that SN-101 recognises specifically the essential epitope by forming multiple hydrogen bonds both with the proximal peptide and GalNAc linked to the threonine residue, concurrently. Remarkably, the structure of the MUC1 glycopeptide in complex with SN-101 is identical to its solution NMR structure, an extended conformation induced by site-specific glycosylation. We demonstrate that this method accelerates dramatically the development of a new class of designated antibodies targeting a variety of “dynamic neoepitopes” elaborated by disease-specific O-glycosylation in the immunodominant mucin domains and mucin-like sequences found in intrinsically disordered regions of many proteins.We developed new class of designated antibodies targeting of “dynamic neoepitopes” elaborated by disease-specific O-glycosylation at the immunodominant mucin domains. 相似文献
3.
Samia Mahouche Nejib Mekni Leila Abbassi Philippe Lang Christian Perruchot Mohamed Jouini Fayna Mammeri Mireille Turmine Hatem Ben Romdhane Mohamed M. Chehimi 《Surface science》2009,603(21):3205-3211
Bis-alkynylated oligoethyleneglycol (OEG) and a monopropargyl-functionalized perfluorinated ethylene glycol (FEG) were clicked to azide-functionalized gold surface (Au–N3) at room temperature via the well known 1,3 cycloaddition click chemical reaction. The Au–N3 substrate was obtained by nucleophilic attack of NaN3 on gold substrates modified by the electrochemical reduction of the , +N2–C6H4–CH2Br diazonium salt. This electrochemical process yields aryl layer-modified gold of the type Au–C6H4–CH2Br (hereafter Au–Br). The untreated and modified gold plates were examined by XPS, PMIRRAS and contact angle measurements. XPS brought evidence for electrografting aryl layers by the detection of Br3d; azide functionalization by the increase of the N/Br atomic ratio; and click reaction of OEG with Au–N3 by the increase of O/N ratio. In addition, the perfluorinated plate (Au-FEG) exhibited F1s and characteristic C1s peaks from -(CF2)7- chain and terminal CF3. Infra red spectroscopy (PMIRRAS) evidenced (i) grafting N3 to Au–Br; (ii) characteristic stretching bands, from ethylene glycol units, C–O–C (1100–1300 cm−1); CF2 (1000–1100 cm−1) and CF3 (1100–1350 cm−1) from FEG grafts; and (iii) suppression of alkynyl bands from OEG and FEG after surface click chemistry. More importantly, PMIRRAS results support an important bridging of the bispropargyl oligoethylene glycol at the gold surface. Water drop contact angles were found to be 48.7° and 83.0° for Au-OEG and Au-FEG, respectively, therefore highlighting the control over the hydrophilic/hydrophobic character of the clicked substrate.This work shows that clicking macromolecules to grafted, diazonium salt-derived aryl layers is a novel, simple and valuable approach for designing robust, functional surface organic coatings. 相似文献
4.
Fast Epitope Mapping for the Anti‐MUC1 Monoclonal Antibody by Combining a One‐Bead‐One‐Glycopeptide Library and a Microarray Platform 下载免费PDF全文
Dr. Fayna Garcia‐Martin Dr. Takahiko Matsushita Dr. Hiroshi Hinou Prof. Dr. Shin‐Ichiro Nishimura 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(48):15891-15902
Anti‐MUC1 monoclonal antibodies (mAbs) are powerful tools that can be used to recognize cancer‐related MUC1 molecules, the O‐glycosylation status of which is believed to affect binding affinity. We demonstrate the feasibility of using a rapid screening methodology to elucidate those effects. The approach involves i) “one‐bead‐one‐compound”‐based preparation of bilayer resins carrying glycopeptides on the shell and mass‐tag tripeptides coding O‐glycan patterns in the core, ii) on‐resin screening with an anti‐MUC1 mAb, iii) separating positive resins by utilizing secondary antibody conjugation with magnetic beads, and (iv) decoding the mass‐tag that is detached from the positive resins pool by using mass spectrometric analysis. We tested a small library consisting of 27 MUC1 glycopeptides with different O‐glycosylations against anti‐MUC1 mAb clone VU‐3C6. Qualitative mass‐tag analysis showed that increasing the number of glycans leads to an increase in the binding affinity. Six glycopeptides selected from the library were validated by using a microarray‐based assay. Our screening provides valuable information on O‐glycosylations of epitopes leading to high affinity with mAb. 相似文献
5.
ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides 总被引:5,自引:0,他引:5
García-Martín F Quintanar-Audelo M García-Ramos Y Cruz LJ Gravel C Furic R Côté S Tulla-Puche J Albericio F 《Journal of combinatorial chemistry》2006,8(2):213-220
CM (ChemMatrix) resin is a new, totally poly(ethylene glycol) (PEG)-based resin, made exclusively from primary ether bonds and, therefore, highly chemically stable. It exhibits good loading and is user-friendly because of its free-flowing form upon drying. It performs excellently for the preparation of hydrophobic, highly structured, and poly-Arg peptides, as compared to polystyrene (PS) resins. In the most striking example, stepwise solid-phase assembly of the highly complex beta-amyloid (1-42) peptide resulted in a crude material of 91% purity. In contrast, literature procedures using PS or PEG-PS-based resins for this peptide required convergent approaches, additional time-consuming steps, or both. In addition to the difficulties of its synthesis, characterization of the beta-amyloid (1-42) peptide as a monomer is also a challenge, and methods for characterization by HPLC and MALDI-TOF have also been developed. 相似文献
6.
Y. Mammeri 《Acta Appl Math》2012,117(1):1-13
We study the periodic solution of a perturbed regularized Boussinesq system (Bona et al., J. Nonlinear Sci. 12:283–318, 2002, Bona et al., Nonlinearity 17:925–952, 2004), namely the system η
t
+u
x
+β(−η
xxt
+u
xxx
)+α((ηu)
x
+ηη
x
+uu
x
)=0,u
t
+η
x
+β(η
xxx
−u
xxt
)+α((ηu)
x
+ηη
x
+uu
x
)=0, with 0<α,β≤1. We prove that the solution, starting from an initial datum of size ε, remains smaller than ε for a time scale of order (ε
−1
α
−1
β)2, whereas the natural time is of order ε
−1
α
−1
β. 相似文献
7.
NMR Spectroscopic Assignment of Backbone and Side‐Chain Protons in Fully Protonated Proteins: Microcrystals,Sedimented Assemblies,and Amyloid Fibrils 下载免费PDF全文
Dr. Jan Stanek Dr. Loren B. Andreas Dr. Kristaps Jaudzems Dr. Diane Cala Dr. Daniela Lalli Andrea Bertarello Dr. Tobias Schubeis Dr. Inara Akopjana Dr. Svetlana Kotelovica Prof. Kaspars Tars Dr. Andrea Pica Dr. Serena Leone Prof. Delia Picone Dr. Zhi‐Qiang Xu Prof. Nicholas E. Dixon Dr. Denis Martinez Mélanie Berbon Nadia El Mammeri Dr. Abdelmajid Noubhani Dr. Sven Saupe Dr. Birgit Habenstein Dr. Antoine Loquet Dr. Guido Pintacuda 《Angewandte Chemie (International ed. in English)》2016,55(50):15504-15509
We demonstrate sensitive detection of alpha protons of fully protonated proteins by solid‐state NMR spectroscopy with 100–111 kHz magic‐angle spinning (MAS). The excellent resolution in the Cα‐Hα plane is demonstrated for 5 proteins, including microcrystals, a sedimented complex, a capsid and amyloid fibrils. A set of 3D spectra based on a Cα–Hα detection block was developed and applied for the sequence‐specific backbone and aliphatic side‐chain resonance assignment using only 500 μg of sample. These developments accelerate structural studies of biomolecular assemblies available in submilligram quantities without the need of protein deuteration. 相似文献
8.
S. Mammeri H. Ammi A. Dib C.A. Pineda-Vargas S. Ourabah M. Msimanga M. Chekirine A. Guesmia 《Radiation Physics and Chemistry》2012,81(12):1862-1866
Stopping power and energy loss straggling data for protons (1H+) and alpha particles (4He+) crossing Formvar thin polymeric foils (thickness of ~0.3 μm) have been measured in the energy range (0.3–2.7) MeV by using the indirect transmission technique. The determined stopping power data were compared to SRIM-2010, PSTAR or ASTAR calculation codes and then analyzed in term of the modified Bethe–Bloch theory to extract the target mean excitation and ionization potential 〈I〉. A resulting value of 〈I〉≈(69.2±1.8) eV was deduced from proton stopping data. The measured straggling data were corrected from surface roughness effects due to target thickness inhomogeneity observed by the atomic force microscopy (AFM) technique. The obtained data were then compared to derived straggling values by Bohr's and Bethe–Livingston's classical theories or by Yang's empirical formula. A deviation of ~40%–80% from the Bohr's straggling value has been observed for all reported energies, suggesting that the Bohr theory cannot be correctly applied to describe the electronic energy loss straggling process with the used low thickness of Formvar foil. The inner-shell contribution of target electrons to energy loss process is also advanced to explain the observed deviation from experiment in case of He+ ions. Finally, the reliability of Bragg's additivity rule was discussed in case of stopping power and straggling results. 相似文献
9.
Mammeri O. A. Hamoud F. Sobina A. A. Ramsh S. M. Fundamensky V. S. Gurzhiy V. V. Khrabrova E. S. 《Russian Journal of General Chemistry》2020,90(11):2043-2047
Russian Journal of General Chemistry - Condensation of 1,3-dialkylthiourea, formaldehyde, and terminal amino acids (C2, C3, or C4) taken in the 1 : 2 : 1 molar ratio has afforded the terminally... 相似文献
10.
Youcef Mammeri 《Applicable analysis》2013,92(12):2526-2535
We study the unique continuation property for the generalized Kadomtsev–Petviashvili (KP) equations and its regularized version. We use Carleman estimates to prove that if the solution of the KP equations vanishes in an open subset, then this solution is identically equal to zero in the horizontal component of the open subset. 相似文献