- Semiconducting Polymer Nano-regulators with Cascading Activation for Photodynamic Cancer Immunotherapy
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Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano-regulator (SPNT) with cascading activation for combinational photodynamic cancer immunotherapy. SPNT comprises an immunoregulator (M-Trp: 1-methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker-cleavable linker. Under near-infrared photoirradiation, SPNT produces singlet oxygen to induce immunogenic apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M-Trp for indoleamine 2,3-dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPNT-mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis.
- He, Shasha,Liu, Jing,Pu, Kanyi,Wang, Jun,Zhang, Chi
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- FLUORESCENTLY LABELED MOLECULES CONTAINING MODIFIED TRYPTOPHAN
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The present disclosure relates to new fluorescent molecules that contain N-alkylated or N-acylated tryptophan and do not substantially quench fluorescent labels attached to the molecules, and the use of such molecules in preparing and studying various compounds, such as substrates and inhibitors for assays of enzymes (e.g., caspases, such as caspase-1 which is an important enzyme in inflammation). An enzyme substrate or enzyme inhibitor that contains a modified tryptophan and fluorescent label as disclosed herein can be studied without loss of signal by F?rster quenching. By reducing or eliminating this quenching, more useful labeled molecules with improved properties for assay development can be prepared.
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Page/Page column 46
(2016/09/15)
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- Inverse γ-Turn-Inspired Peptide: Synthesis and Analysis of Segetalin A Indole Hemiaminal
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Substitution of a peptide bond for an imine transforms the irreversible macrocyclization of peptides into a reversible process. The inherent cyclization tendency of a linear peptide is then analyzable through the equilibrium between the aldehyde and the imine by virtue of the higher reactivity of the corresponding linear peptide aldehyde. The tryptophan side chain of segetalin A aldehyde forms a 12-membered cyclic indole hemiaminal instead of the 18-membered macrocyclic imine expected. Herein, we analyzed this uncommon hemiaminal that shows that the biosynthesis of cyclic peptides is not necessarily based on linear precursor peptides with a high inherent macrolactamization tendency. By substituting a peptide bond for an imine, the cyclization tendency of a linear peptide can be analyzed through equilibration of the aldehyde and imine forms. The tryptophan side chain of segetalin A aldehyde forms a 12-membered cyclic indole hemiaminal instead of the expected 18-membered macrocyclic imine. Herein, we analyze this uncommon hemiaminal.
- Lamping, Matthias,Enck, Sebastian,Geyer, Armin
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p. 7443 - 7448
(2016/01/26)
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- Self-assembled surfactant cyclic peptide nanostructures as stabilizing agents
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A number of cyclic peptides including [FR]4, [FK]4, [WK]5, [CR]4, [AK]4, and [WR]n (n = 3-5) containing l-amino acids were produced using solid-phase peptide synthesis. We hypothesized that an optimal balance of hydrophobicity and charge could generate self-assembled nanostructures in aqueous solution by intramolecular and/or intermolecular interactions. Among all the designed peptides, [WR] n (n = 3-5) generated self-assembled vesicle-like nanostructures at room temperature as shown by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and/or dynamic light scattering (DLS). This class of peptides represents the first report of surfactant-like cyclic peptides that self-assemble into nanostructures. A plausible mechanistic insight into the self-assembly of [WR]5 was obtained by molecular modeling studies. Modified [WR]5 analogues, such as [WMeR]5, [WR(Me)2]5, [WMeR(Me)2]5, and [WdR]5, exhibited different morphologies to [WR]5 as shown by TEM observations. [WR]5 exhibited a significant stabilizing effect for generated silver nanoparticles and glyceraldehyde-3-phosphate dehydrogenase activity. These studies established a new class of surfactant-like cyclic peptides that self-assembled into nanostructures and could have potential applications for the stabilization of silver nanoparticles and protein biomolecules.
- Mandal, Dindyal,Tiwari, Rakesh K.,Nasrolahi Shirazi, Amir,Oh, Donghoon,Ye, Guofeng,Banerjee, Antara,Yadav, Arpita,Parang, Keykavous
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p. 9465 - 9475
(2013/10/01)
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- Small molecules for treatment of hypercholesterolemia and related diseases
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The present invention provides compositions adapted to enhance reverse cholesterol transport in mammals. The compositions are suitable for oral delivery and useful in the treatment and/or prevention of hypercholesterolemia, atherosclerosis and associated cardiovascular diseases.
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Page/Page column 24-25
(2010/02/15)
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- Investigation of the PDZ domain ligand binding site using chemically modified peptides
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Several chemically modified analogues to a tightly binding ligand for the second PDZ domain of MAGI-3 were synthesized and evaluated for their ability to compete with native peptide ligands. N-methyl scanning of the ligand backbone amides revealed the energetically important hydrogen bonds between the ligand backbone and the PDZ domain. Analogues to the ligand's conserved threonine/serine(-2) residue, involved in a side chain to side chain hydrogen bond with a conserved histidine in the PDZ domain, revealed that the interaction is highly sensitive to the steric structure around the hydroxyl group of this residue. Analogues of the ligand carboxy terminus revealed that the full hydrogen bond network of the GLGF loop is important in ligand binding.
- Novak, Kathleen A.P,Fujii, Naoaki,Guy
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p. 2471 - 2474
(2007/10/03)
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