125923-10-6Relevant articles and documents
New maleimide spirobenzopyran derivatives as photochromic labels for macromolecules with sulfhydryl groups
Laptev, Alexey V.,Lukin, Alexey Yu.,Belikov, Nikolay E.,Demina, Olga V.,Khodonov, Andrey A.,Shvets, Vitalii I.
, p. 245 - 246 (2014)
Two new photochromic labels of spiro[chromene-2,2'-indole] series supplied with 5-positioned maleimide moieties suitable for labelling macromolecules with sulfhydryl groups were synthesized.
67/68Ga-labeling agent that liberates 67/68Ga-NOTA-methionine by lysosomal proteolysis of parental low molecular weight polypeptides to reduce renal radioactivity levels
Uehara, Tomoya,Rokugawa, Takemi,Kinoshita, Mai,Nemoto, Souki,Fransisco Lazaro, Guerra Gomez,Hanaoka, Hirofumi,Arano, Yasushi
, p. 2038 - 2045 (2014)
The renal localization of gallium-67 or gallium-68 (67/68Ga)-labeled low molecular weight (LMW) probes such as peptides and antibody fragments constitutes a problem in targeted imaging. Wu et al. previously showed that 67Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bz-NOTA)-conjugated methionine (67Ga-NOTA-Met) was rapidly excreted from the kidney in urine following lysosomal proteolysis of the parental 67Ga-NOTA-Bz-SCN-disulfide-stabilized Fv fragment (Bioconjugate Chem., (1997) 8, 365-369). In the present study, a new 67/68Ga-labeling reagent for LMW probes that liberates 67/68Ga-NOTA-Met was designed, synthesized, and evaluated using longer-lived 67Ga in order to reduce renal radioactivity levels. We employed a methionine-isoleucine (MI) dipeptide bond as the cleavable linkage. The amine residue of MI was coupled with SCN-Bz-NOTA for 67Ga-labeling, while the carboxylic acid residue of MI was derivatized to maleimide for antibody conjugation in order to synthesize NOTA-MI-Mal. A Fab fragment of the anti-Her2 antibody was thiolated with iminothiolane, and NOTA-MI-Mal was conjugated with the antibody fragment by maleimide-thiol chemistry. The Fab fragment was also conjugated with SCN-Bz-NOTA (NOTA-Fab) for comparison. 67Ga-NOTA-MI-Fab was obtained at radiochemical yields of over 95% and was stable in murine serum for 24 h. In the biodistribution study using normal mice, 67Ga-NOTA-MI-Fab registered significantly lower renal radioactivity levels from 1 to 6 h postinjection than those of 67Ga-NOTA-Fab. An analysis of urine samples obtained 6 h after the injection of 67Ga-NOTA-MI-Fab showed that the majority of radioactivity was excreted as 67Ga-NOTA-Met. In the biodistribution study using tumor-bearing mice, the tumor to kidney ratios of 67Ga-NOTA-MI-Fab were 4 times higher (6 h postinjection) than those of 67Ga-NOTA-Fab. Although further studies including the structure of radiometabolites and/or cleavable linkages are required, the results of the present study indicate that the current chemical design is applicable to the development of 67Ga-labeled Fabs for low renal radioactivity levels.
Multivalent design of apoptosis-inducing Bid-BH3 peptide-oligosaccharides boosts the intracellular activity at identical overall peptide concentrations
Richter, Martin,Chakrabarti, Alokta,Ruttekolk, Ivo R.,Wiesner, Burkhard,Beyermann, Michael,Brock, Roland,Rademann, J?rg
, p. 16708 - 16715 (2012)
Multivalent peptide-oligosaccharide conjugates were prepared and used to investigate the multivalency effect concerning the activity of Bid-BH3 peptides in live cells. Dextran oligosaccharides were carboxyethylated selectively in the 2-position of the carbohydrate units and activated for the ligation of N-terminally cysteinylated peptides. Ligation through maleimide coupling was found to be superior to the native chemical ligation protocol. Monomeric Bid-BH3 peptides were virtually inactive, whereas pentameric peptide conjugates induced apoptosis up to 20-fold stronger at identical peptide concentrations. Comparison of lowly multivalent and highly multivalent peptide dextrans proved a multivalency effect in life cells which was specific for the BH3 peptide sequence. A potent blend of sugar and peptides: The intracellular activity of BH3 peptides is boosted upon their multivalent presentation on the oligosaccharide dextran. Induction of apoptosis by the pentavalent BH3 peptide dextran was visualized in cells of the human cell line Jurkat E6.1. by using a protein stain Annexin-V (purple; see figure). This flexible access to peptide dextrans should pave the way to further biological applications of these new materials. Copyright
Design and synthesis of thiol-reactive lipopeptides
Boeckler, Christophe,Frisch, Benoit,Schuber, Francis
, p. 2055 - 2058 (1998)
Lipopeptides are potent adjuvants that trigger an immune response against covalently conjugated low molecular mass antigens. We report here the design and synthesis of thiol-reactive lipopeptides (6, 7) which can be incorporated into liposomes and react, under mild conditions, with synthetic peptides carrying a thiol function.
The versatility of N-alkyl-methoxyamine bi-functional linkers for the preparation of glycoconjugates
Munneke, Stefan,Dangerfield, Emma M.,Stocker, Bridget L.,Timmer, Mattie S. M.
, p. 633 - 642 (2017)
The application of N-glycosyl-N-alkyl-methoxyamine bi-functional linkers for the synthesis of a variety of glycoconjugates is described. The linker contains a specific functional group, such as an amine, azide, thiol, or carboxylic acid, which can be used for conjugation methodologies that include amide ligation, sulfonylation, copper-mediated Huisgen cycloaddition or thiol-maleimide coupling. In this way, glycoconjugates equipped with biotin, a fluorescent reporter, or a protein were efficiently synthesised, thus demonstrating the versatility of this type of oxyamine linker for the construction of glycoconjugate probes.
Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes
Becker, Bastian,Englert, Simon,Schneider, Hendrik,Yanakieva, Desislava,Hofmann, Sarah,Dombrowsky, Carolin,Macarrón Palacios, Arturo,Bitsch, Sebastian,Elter, Adrian,Meckel, Tobias,Kugler, Benedikt,Schirmacher, Anastasyia,Avrutina, Olga,Diederichsen, Ulf,Kolmar, Harald
, (2021)
The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell-penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell-impermeable cargo molecules. For many CPPs, multimerization or multicopy arrangement on a scaffold resulted in improved delivery but also higher cytotoxicity. Recently, we introduced dextran as multivalent, hydrophilic polysaccharide scaffold for multimerization of cell-targeting cargoes. Here, we investigated covalent conjugation of a CPP to dextran in multiple copies and assessed the ability of resulted molecular hybrid to enter the cytoplasm of mammalian cells without largely compromising cell viability. As a CPP, we used a novel, low-toxic cationic amphiphilic peptide L17E derived from M-lycotoxin. Here, we show that cell-penetrating properties of L17E are retained upon multivalent covalent linkage to dextran. Dextran-L17E efficiently mediated cytoplasmic translocation of an attached functional peptide and a peptide nucleic acid (PNA). Moreover, a synthetic route was established to mask the lysine side chains of L17E with a photolabile protecting group thus opening avenues for light-triggered activation of cellular uptake.
Anisotropic dynamics and mechanics of macromolecular crystals containing lattice-patterned polymer networks
Han, Kenneth,Bailey, Jake B.,Zhang, Ling,Tezcan, F. Akif
, p. 19402 - 19410 (2020)
The mechanical and functional properties of many crystalline materials depend on cooperative changes in lattice arrangements in response to external perturbations. However, the flexibility and adaptiveness of crystalline materials are limited. Additionally, the bottom-up, molecular-level design of crystals with desired dynamic and mechanical properties at the macroscopic level remains a considerable challenge. To address these challenges, we had previously integrated mesoporous, cubic ferritin crystals with hydrogel networks, resulting in hybrid materials (polymer-integrated crystals or PIX) which could undergo dramatic structural changes while maintaining crystalline periodicity and display efficient self-healing. The dynamics and mechanics of these ferritin-PIX were devoid of directionality, which is an important attribute of many molecular and macroscopic materials/devices. In this study, we report that such directionality can be achieved through the use of ferritin crystals with anisotropic symmetries (rhombohedral or trigonal), which enable the templated formation of patterned hydrogel networks in crystallo. The resulting PIX expand and contract anisotropically without losing crystallinity, undergo prompt bending motions in response to stimuli, and self-heal efficiently, capturing some of the essential features of sophisticated biological devices like skeletal muscles.
Efficient solid phase extraction of codeine from human urine samples using a novel magnetic molecularly imprinted nanoadsorbent and its spectrofluorometric determination
Madrakian, Tayyebeh,Fazl, Fariba,Ahmadi, Mazaher,Afkhami, Abbas
, p. 122 - 129 (2016)
From a medical or clinical point of view, to assess toxicity, adverse effects, interactions and therapeutic efficiency, monitoring drug levels in body fluids, such as urine and plasma, has become increasingly necessary. This study reports on a novel method for determination of trace concentration levels of codeine phosphate in human urine samples. In this regard, a solid phase extraction step, based on a novel magnetic molecularly imprinted polymer nanoadsorbent, has been developed to be used prior to spectrofluorometric analysis of the drug. After optimization of various factors, such as pH, contact time, adsorbent dosage and desorbing solvent, the results showed that using the proposed method sensitive and accurate determination of the drug in the concentration range of 2.0-500.0 ng mL-1 with the detection limit of 0.67 ng mL-1 is achievable. The urine sample analysis results show that a powerful method for codeine phosphate determination has been proposed.
An endoplasmic reticulum-targeted organic photothermal agent for enhanced cancer therapy
Wang, Kaiye,Xiang, Yanan,Pan, Wei,Wang, Hongyu,Li, Na,Tang, Bo
supporting information, p. 793 - 797 (2021/09/15)
Developing selectively targeted photothermal agents to reduce side effects in photothermal therapy remains a great challenge. Inspired by the key role of endoplasmic reticulum in the protein synthesis and intracellular signal transduction, particularly for the immunogenic cell death induced by endoplasmic reticulum stress, we developed an endoplasmic reticulum-targeted organic photothermal agent (Ts-PT-RGD) for enhancing photothermal therapy of tumor. The photothermal agent was covalently attached with 4-methylbenzenesulfonamide and cyclic Arg-Gly-Asp (cRGD) peptide for realizing the targeting of endoplasmic reticulum and tumor cell. Owing to its amphiphilic properties, it readily self-assembles in water to form nanoparticles. The photothermal agent possesses excellent photophysical properties and biological compatibility. In vitro and in vivo experiments demonstrate that it can actively target endoplasmic reticulum and effectively ablate tumor with near-infrared laser.
Hierarchical protein self-assembly into dynamically controlled 2D nanoarraysviahost-guest chemistry
Chen, Hongwei,Hou, Chunxi,Li, Fei,Li, Yijia,Liu, Junqiu,Luo, Quan,Tian, Ruizhen,Xu, Jiayun,Zhao, Linlu
supporting information, p. 10620 - 10623 (2021/10/19)
A dynamically reversible two-dimensional (2D) protein assembly system was designed based on host-guest interactions and was triggered to disassembleviaa competition mechanism. The artificially tunable and reversible protein assembly architectures hold great potential for on/off switches in bio-systems.
