- Polycysteine as a new type of radio-protector ameliorated tissue injury through inhibiting ferroptosis in mice
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Amifostine has been the only small molecule radio-protector approved by FDA for decades; however, the serious adverse effects limit its clinical use. To address the toxicity issues and maintain the good potency, a series of modified small polycysteine peptides had been prepared. Among them, compound 5 exhibited the highest radio-protective efficacy, the same as amifostine, but much better safety profile. To confirm the correlation between the radiation-protective efficacy and the DNA binding capability, each of the enantiomers of the polycysteine peptides had been prepared. As a result, the l-configuration compounds had obviously higher efficacy than the corresponding d-configuration enantiomers; among them, compound 5 showed the highest DNA binding capability and radiation-protective efficacy. To our knowledge, this is the first study that has proved their correlations using direct comparison. Further exploration of the mechanism revealed that the ionizing radiation (IR) triggered ferroptosis inhibition by compound 5 could be one of the pathways for the protection effect, which was different from amifostine. In summary, the preliminary result showed that compound 5, a polycysteine as a new type of radio-protector, had been developed with good efficacy and safety profile. Further study of the compound for potential use is ongoing.
- Zhang, Junling,Li, Kui,Zhang, Qianru,Zhu, Zhimei,Huang, Gongchao,Tian, Hongqi
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- Tripeptide-induced modulation of mesenchymal stem cell biomechanics stimulates proliferation and wound healing
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We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs). Notably, Young's modulus of peptide-treated hMSCs was found to be ~2 fold higher compared to the control group. These peptides promoted wound healing in hMSCs, without stimulating osteogenic and adipogenic differentiation, thus showing high potential in vascular tissue engineering applications.
- Ali, Rafat,Chattopadhyay, Naibedya,Kulkarni, Chirag,Kulkarni, Manish M.,Porwal, Konica,Sharma, Swati,Tewari, Deepshikha,Verma, Sandeep
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supporting information
p. 3043 - 3046
(2020/03/18)
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- Initial Analysis of the Arylomycin D Antibiotics
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The arylomycins are a class of natural product antibiotics that inhibit bacterial type I signal peptidase and are under development as therapeutics. Four classes of arylomycins are known, arylomycins A-D. Previously, we reported the synthesis and analysis of representatives of the A, B, and C classes and showed that their spectrum of activity has the potential to be much broader than originally assumed. Along with a comparison of the mechanism of acquired and innate resistance, this led us to suggest that the arylomycins are latent antibiotics, antibiotics that once possessed broad-spectrum activity, but which upon examination today, have only narrow spectrum activity due to prior selection for resistance in the course of the competition with other microorganisms that drove their evolution in the first place. Interestingly, actinocarbasin, the only identified member of the arylomycin D class, has been reported to have activity against MRSA. To confirm and understand this activity, several actinocarbasin derivatives were synthesized. We demonstrate that the previously reported structure of actinocarbasin is incorrect, identify what is likely the correct scaffold, confirm that scaffold has activity against MRSA, and determine the origin of this activity.
- Forli, Stefano,Holcomb, Matthew,Peters, David S.,Romesberg, Floyd E.,Santos-Martins, Diogo,Tan, Yun Xuan,Walsh, Shawn I.
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supporting information
p. 2112 - 2121
(2020/08/10)
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- CGG repeat DNA assisted dimerization of CGG/CGG binding molecule through intermolecular disulfide formation
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A new DNA binding small molecule, NCD-CC is reported. NCD-CC has a NCD domain, which recognizes the G-G mismatch in a CGG/CGG triad, and a cysteinylcystein (CC) moiety. Dimerization of NCD-CC through intermolecular disulfide bond formation was accelerated in the presence of CGG repeat DNA.
- Yamada, Takeshi,Miki, Shouta,Ni, Lu,Nakatani, Kazuhiko
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supporting information
p. 13072 - 13075
(2018/11/30)
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- Aminothiol compound, preparation method of aminothiol compound and application of aminothiol compound in radiation protection
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The invention discloses an aminothiol compound, a preparation method of the aminothiol compound and application of the aminothiol compound in radiation protection. The compound has a structure shown in the formula I in the description, wherein A1 is selected from -C(O)NR8-, -S(O)2-NR8-, -S(O)NR8- and -R7-NR8-, A2 is selected from carbonyl, sulfonyl, sulfinyl and substituted or unsubstituted C1-6 alkyl, R1, R2, R5 and R6 can be the same or not and are selected from hydrogen and substituted or unsubstituted C1-C5 alkyl or hetero alkyl, n is an integer from 0 to 20000, R3 and R4 are independently selected from hydrogen, X and substituted or unsubstituted C1-6 alkyl, X is selected from F, Cl, Br and I, R7 is selected from substituted or unsubstituted C1-C6 alkyl, and R8 is selected from hydrogen and substituted or unsubstituted C1-C6 alkyl. The compound has the effect of reducing biological injury caused by ionizing radiation and also has the effects of prolonging the lifetime of radiated animals and increasing the survival rate of the radiated animals.
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Paragraph 0096; 0100; 0101; 0102; 0142; 0146; 0147; 0148
(2017/04/03)
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- Multifunctional imaging cross-linked stable nanometer drug-loading micelles and preparation method thereof
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The present invention discloses multifunctional imaging cross-linked stable nanometer drug-loading micelles and a preparation method thereof. The preparation method comprises: adding 200 mg of an amphiphilic drug carrier mPEG-S-Trityl-Cys-Dopa and a hydrophobic anti-cancer drug to an organic solvent, dissolving, and carrying out dialysis by using a dialysis bag to remove free Fe; carrying out centrifugation, and filtering the supernatant by using a 0.45 [mu]m microporous filtration membrane; and carrying out freeze drying on the filtrate, wherein the freeze-dried product is the multifunctional imaging cross-linked stable nanometer drug-loading micelles mPEG-S-Trityl-Cys-Dopa-Fe/hydrophobic anti-cancer drug. According to the present invention, the obtained nanometer micelles have the stability and the pH-sensitivity, and can be visible by MRI, can break through the single-function mode of the traditional drug delivery system, can integrate the MRI imaging function and the drug carrier function, and can achieve the synchronous diagnosis and treatment of cancers.
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Paragraph 0075; 0077
(2017/12/28)
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- PROCESS FOR PREPARING EPTIFIBATIDE
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The present invention provides processes for preparation of eptifibatide that involve coupling of amino acids in a (2+5), (4+3) and (3+4) sequence method. The invention further provides products produced by the described processes, novel compounds that can be used as synthetic intermediates for the preparation of eptifibatide.
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Page/Page column
(2014/06/24)
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- A tetrazine templated method for the synthesis of ternary conjugates
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Conjugation is an important reaction that enables coupling of molecules. Many protocols exist for the synthesis of binary conjugates from two different molecules or for the polyvalent display of a single molecule. There aren't many methods for the synthesis of ternary conjugates. However, methods for ternary conjugation are important for understanding the interplay of interactions between three biomolecules (or any three molecules per se). A strategy for ternary bioconjugation using inverse electron demand Diels-Alder reaction with tetrazine is studied. Ternary conjugation was demonstrated by the reaction of a model glyco-peptide binary conjugate with a fluorescent tagged olefin. The Royal Society of Chemistry 2013.
- Venkateswara Rao, Boddu,Dhokale, Snehal,Rajamohanan, Pattuparambil R.,Hotha, Srinivas
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supporting information
p. 10808 - 10810
(2013/11/06)
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- Novel molecular combination deriving from natural aminoacids and polyphenols: Design, synthesis and free-radical scavenging activities
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Following the recent output of scientific publications in the matter of synergic activity between different antioxidants, we have undertaken the present study with the aim to synthesize new molecules with radical-scavengers activity based on the conjugation of bioactive portions (i.e. phenols, cysteine, methionine or tyrosine), characterized by different structures and mechanisms of action, to promote the simultaneous quenching of different radical species in the site of the oxidative damage. In this context, derivatives of phenolic acid, aminoacids and dopamine have been also prepared. The newly synthesized compounds were evaluated in vitro applying specific and complementary antioxidant test such as DPPH assay and ORAC test. As emerged from the evaluation, prerequisites for the activity of the synthesized molecules were: i) the maintenance of at least two hydroxylic groups on the aromatic moiety of phenolic portion, ii) the presence of a spacer between the aromatic moiety and the carbonilic group.
- Silvia, Vertuani,Baldisserotto, Anna,Scalambra, Emanuela,Malisardi, Gemma,Durini, Elisa,Manfredini, Stefano
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experimental part
p. 383 - 392
(2012/07/28)
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- CYSTEINE AND CYSTINE BIOISOSTERES TO TREAT SCHIZOPHRENIA AND REDUCE DRUG CRAVINGS
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The present invention provides cysteine and cystine bioisosteres for the treatment of schizophrenia and drug addiction. The invention further encompasses pharmaceutical compositions containing such bioisosteres and methods of using the bioisosteres for treatment of schizophrenia and drug addiction.
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Page/Page column 30; 31
(2010/01/29)
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- 3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists
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A series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were prepared and evaluated as potential allosteric modulators at the A1 adenosine receptor. The structure-activity relationships of the 3- and 6-positions of a series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were explored. Despite finding that 3- and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines possess the ability to recognize an allosteric site on the agonist-occupied A1AR at relatively high concentrations, the structural modifications we have performed on this scaffold favor the expression of orthosteric antagonist properties over allosteric properties. This research has identified 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as novel class of orthosteric antagonist of the A1AR and highlighted the close relationship between structural elements governing allosteric modulation and orthosteric antagonism of agonist function at the A1AR.
- Aurelio, Luigi,Valant, Celine,Figler, Heidi,Flynn, Bernard L.,Linden, Joel,Sexton, Patrick M.,Christopoulos, Arthur,Scammells, Peter J.
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experimental part
p. 7353 - 7361
(2010/03/03)
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- Dynamic combinatorial libraries of disulfide cages in water
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(Figure Presented) Dynamic combinatorial libraries (DCLs) containing water-soluble disulfide-linked cages (alongside macrocyclic structures) have been generated and characterized. Unlike most other strategies for generating molecular cages, the structures are held together by covalent bonds, which are formed under thermodynamic control. The diversity of the cages generated opens new possibilities for a generalized combinatorial strategy toward molecular encapsulation.
- West, Kevin R.,Bake, Kyle D.,Otto, Sijbren
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p. 2615 - 2618
(2007/10/03)
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