- Orthogonal enzymatic reactions to control supramolecular hydrogelations
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Enzyme-responsive hydrogels have great potential in applications of controlled drug release, tissue engineering, etc. In this study, we reported on a supramolecular hydrogel that showed responses to two enzymes, phosphatase which was used to form the hydrogels and esterase which could trigger gel-sol phase transitions. The gelation process and visco-elasticity property of the resulting gel, morphology of the nanostructures in hydrogel, and peptide conformation in the self-assembled nanostructure were characterized by rheology, transmission electron microscope (TEM), and circular dichroism (CD), respectively. Potential application of the enzyme-responsive hydrogel in drug release was also demonstrated in this study. Though only one potential application of drug release was proved in this study, the responsive hydrogel system in this study might have potentials for the applications in fields of cell culture, controlled-drug release, etc. Copyright
- Chen, Guoqin,Ren, Chunhua,Wang, Ling,Xu, Bing,Yang, Zhimou
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Read Online
- Synthesis and anticancer activities of proline-containing cyclic peptides and their linear analogs and congeners
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A solution phase method was adopted for the synthesis of proline-containing cyclic pentapeptide 2 and total synthesis of naturally occurring cyclic heptapeptide Reniochalistatin B 3. For the synthesis of 3, both divergent and convergent strategies were used to improve the overall yield from 12 to 25%. Different N and C terminal modified linear analogs and congeners of 2 and 3 were synthesized. Both cyclic peptides 2 and 3 and their linear analogs/congeners were evaluated for anti-cancer activity against HeLa cell line, among which pentapeptide 2 h and hexapeptide 3n with N-terminal protected hexafluoroisopropyl carbamates (HFIPC) interestingly showed higher cytotoxicity with an IC50 of 2.73 and 4.3 μM, respectively compared to their Boc-protected analogs 2a (IC50 20 μM) and 3c (IC50 38.51 μM) and cyclic peptides 2 (>100 μM) and 3 (47 μM). These results were further validated by biological experiments such as colony formation and wound healing assays.
- Ghosh, Keshab Ch,Duttagupta, Indranil,Bose, Chandra,Banerjee, Priyanjalee,Gayen, Anuran Kumar,Sinha, Surajit
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supporting information
p. 221 - 236
(2019/01/19)
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- Efficient Building Blocks for Solid-Phase Peptide Synthesis of Spin Labeled Peptides for Electron Paramagnetic Resonance and Dynamic Nuclear Polarization Applications
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Specific spin labeling allows the site-selective investigation of biomolecules by EPR and DNP enhanced NMR spectroscopy. A novel spin labeling strategy for commercially available Fmoc-amino acids is developed. In this approach, the PROXYL spin label is covalently attached to the hydroxyl side chain of three amino acids hydroxyproline (Hyp), serine (Ser) and tyrosine (Tyr) by a simple three-step synthesis route. The obtained PROXYL containing building-blocks are N-terminally protected by the Fmoc-protection group, which makes them applicable for the use in solid-phase peptide synthesis (SPPS). This approach allows the insertion of the spin label at any desired position during SPPS, which makes it more versatile than the widely used post synthetic spin labeling strategies. For the final building-blocks, the radical activity is proven by EPR. DNP enhanced solid-state NMR experiments employing these building-blocks in a TCE solution show enhancement factors of up to 26 for 1H and 13C (1H→13C cross-polarization). To proof the viability of the presented building-blocks for insertion of the spin label during SPPS the penta-peptide Acetyl-Gly-Ser(PROXYL)-Gly-Gly-Gly was synthesized employing the spin labeled Ser building-block. This peptide could successfully be isolated and the spin label activity proved by EPR and DNP NMR measurements, showing enhancement factors of 12.1±0.1 for 1H and 13.9±0.5 for 13C (direct polarization).
- Brodrecht, Martin,Herr, Kevin,Bothe, Sarah,de Oliveira, Marcos,Gutmann, Torsten,Buntkowsky, Gerd
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p. 1475 - 1487
(2019/05/22)
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- A gene vaccine carrier, preparation method and application thereof
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The invention discloses a gene vaccine vector, and a preparation method and an application thereof; the gene vaccine vector is a supramolecular hydrogel formed through phosphatase catalysis of a small-molecular peptide; the small-molecular peptide has the structural formula represented by the formula (I), wherein when m=1, n=0, 1, 2 or 3; when n=1, m=1, 2 or 3. The gene vaccine vector after being loaded with DNA has the advantages of strong immunogenicity, large load capacity, no obvious toxicity and injectable immunity. The gene vaccine vector is mild in preparation conditions and simple in process.
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Paragraph 0036; 0038; 0040; 0041
(2017/08/26)
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- Synthesis of BODIPY-Labeled Cholesterylated Glycopeptides by Tandem Click Chemistry for Glycocalyxification of Giant Unilamellar Vesicles (GUVs)
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The glycocalyx cover membrane surfaces of all living cells. These complex architectures render their interaction mechanisms on the membrane surface difficult to study. Artificial cell-sized membranes with selected and defined glycosylation patterns may serve as a minimalistic approach to systematically study cell surface glycan interactions. The development of a facile general synthetic procedure for the synthesis of BODIPY-labeled cholesterylated glycopeptides, which can coat cell-size giant unilamellar vesicles (GUVs), is described. These peptide constructs were synthesized by: 1) solid-phase peptide synthesis (SPPS) using cholesterylated Fmoc-amino acids (Fmoc=9-fluorenylmethoxycarbonyl) followed by tandem click reactions, 2) attachment of a BODIPY-bicyclononyne (BCN) (prepared by Mitsunobu chemistry via novel aryl BCN-ethers) in the absence of a catalyst, and 3) glycosylation by means of copper(I)-catalyzed click reaction of an azidoglycan. Seven different GUV-glycoforms were prepared and four of these were evaluated with their corresponding four specific anti-glycan binding lectins.
- Stuhr-Hansen, Nicolai,Vagianou, Charikleia-Despoina,Blixt, Ola
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supporting information
p. 9472 - 9476
(2017/07/22)
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- Enzyme-controllable F-NMR turn on through disassembly of peptide-based nanospheres for enzyme detection
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The enzyme tyrosinase could trigger the disassembly of peptide-based nanospheres, resulting in F-NMR signal turning on.
- Gao, Jie,Shi, Yang,Wang, Youzhi,Cai, Yanbin,Shen, Jie,Kong, Deling,Yang, Zhimou
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supporting information
p. 1383 - 1386
(2014/03/21)
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- Self-assembled nanospheres as a novel delivery system for taxol: A molecular hydrogel with nanosphere morphology
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Here we reported on the first example of a Folic acid-based molecular hydrogel with nanosphere morphology as a delivery system for Taxol.
- Wang, Huaimin,Yang, Cuihong,Wang, Ling,Kong, Deling,Zhang, Yongjun,Yang, Zhimou
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supporting information; experimental part
p. 4439 - 4441
(2011/06/27)
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- PHOSPHONATED RIFAMYCINS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
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The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.
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Page/Page column 125-126
(2010/04/03)
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- Efficient solid-phase synthesis of sulfotyrosine peptides using a sulfate protecting-group strategy
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(Chemical Equation Presented) Double protection: Efficient Fmoc-based solid-phase synthesis (SPPS) of sulfotyrosine (sY) peptides is achieved by incorporating the sY residue(s) as a dichlorovinyl-protected (DCV) sulfodiester(s) and using 2-methylpiperidine for Fmoc removal. After removal of the other protecting groups, the DCV group could be cleaved by mild hydrogenolysis giving the sY peptides in good yield.
- Ali, Ahmed M.,Taylor, Scott D.
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supporting information; experimental part
p. 2024 - 2026
(2009/07/25)
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- Designed amino acid ATRP initiators for the synthesis of biohybrid materials
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A synthetic strategy to prepare peptide-polymer conjugates with precise sites of attachment is described. Amino acids modified with atom transfer radical polymerization (ATRP) initiators for the polymerization of styrenes and hacrylates were prepared. Fmoc-4-(1-chloroethyl)-phenylalanine (5) was synthesized in four steps from Fmoc-tyrosine. HATU-mediated amidation with glycine-OMe resulted in dipeptide (6). The initiator was effective for Cu(I)/bipyridine mediated bulk polymerization of styrene. Kinetic studies indicated a controlled polymerization, with high conversion (97%), and a polydispersity index (PDI) of 1.25. Fmoc-O-(2-bromoisobutyryl)-serine tert-butyl ester (10) was synthesized from Fmoc-Ser(OTrt)-OH in three steps. This initiator was employed in the ATRP of 2-hydroxyethyl methacrylate (HEMA), and kinetic studies indicated a controlled polymerization. Different monomer to initiator ratios resulted in poly-(HEMA) of different molecular weights and narrow PDIs (1.14-1.25). Conversions were between 70 and 99%. HEMA modified with N-acetyl-D-glucosamine (GlcNAc) was also polymerized to 84% conversion and the resulting PDI was 1.19. The t-butyl ester protecting group of 10 was removed, and the resulting amino acid (11) was incorporated into VM(H)VVQTK by standard solid-phase peptide synthesis. Polymerization resulted in the glycopolymer-peptide conjugate in 93% conversion and a PDI of 1.14.
- Broyer, Rebecca M.,Quaker, Grace M.,Maynard, Heather D.
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p. 1041 - 1047
(2008/09/20)
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- Caged phospho-amino acid building blocks for solid-phase peptide synthesis
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Three 1-(2-nitrophenyl)ethyl-caged phosphoamino acids have been synthesized for use in standard Nα-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (SPPS). The most common naturally occurring phosphoamino acids, serine, threonine, and tyrosine, were prepared as protected caged building blocks by modification with a unique phosphitylating reagent. In previous work, caged phospho-peptides were made using an interassembly approach (Rothman, D. M.; Vazquez, M. E.; Vogel, E. M.; Imperiali, B. Org. Lett. 2002, 4, 2865-2868). However, this technique is limited to creating peptides without oxidation sensitive residues C-terminal to the amino acid to be modified and the methodology involves synthetic manipulations on the solid phase that may limit the utilization of the methodology. Herein we report the facile synthesis of N-α-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-serine 1, N-α-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-threonine 2, and N-α-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-tyrosine 3. These building blocks allow the synthesis of any caged phospho-peptide sequence using standard Fmoc-based SPPS procedures.
- Rothman, Deborah M.,Vazquez, M. Eugenio,Vogel, Elizabeth M.,Imperiali, Barbara
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p. 6795 - 6798
(2007/10/03)
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- 2-Phenyl isopropyl and t-butyl trichloroacetimidates: Useful reagents for ester preparation of N-protected amino acids under neutral conditions
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2-Phenylisopropyl and t-butyl trichloroacetamidates 1 and 2 are useful reagents for the esterification of N-protected aminoacids under mild neutral conditions. In the case of hydroxyl-containing amino acids dialkylation occurs but no selectivity could be obtained.
- Thierry, Josiane,Yue, Chongwei,Potier, Pierre
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p. 1557 - 1560
(2007/10/03)
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- L-O-(2-malonyl)tyrosine (L-OMT) a new phosphotyrosyl mimic suitably protected for solidphase synthesis of signal transduction inhibitory peptides
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A new phosphotyrosyl (pTyr) mimic L-O-(2-malonyl)tyrosine (L-OMT, 4) utilizes a malonyl structure in place of the parent phosphate group. This compound is stable to protein-tyrosine phosphatases and has advantages over phosphonate-based pTyr mimics in that protection of the malonyl group as its diester allows passage of the OMT across cell membranes, with subsequent esterase-mediated liberation of the free diacid once inside cells. Herein is reported the synthesis of Nα-Fmoc-L-OMT-O,O-(ferf-butyl)2 (5) for the solid-phase synthesis of L-OMT containing peptides as modulators of cellular signal transduction. Additionally included is the preparation of Nα-Fmoc-L-OMT-O,O-(n-butyl)2 (6) for the direct solid-phase synthesis of OMT-peptide diester prodrugs for use in cell-based studies.
- Ye, Bin
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p. 4733 - 4736
(2007/10/02)
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