Browsing by Subject "Ligands"

Now showing 1 - 6 of 6

Open Access
Design strategies for ratiometric chemosensors: modulation of excitation energy transfer at the energy donor site
(2009) Guliyev, R.; Coskun, A.; Akkaya, E. U.
Excitation energy transfer, when coupled to an ion-modulated ICT chromophore, creates novel opportunities in sensing. The direction of energy transfer and the point of ICT modulation can be varied as desired. In our previous work, we have shown that energy transfer efficiency between two energetically coupled fluorophores will be altered by the metal ion binding to the ICT chromophore carrying a ligand. There are two beneficial results: increased pseudo-Stokes shift and expanded dynamic range. Here, we explored the consequences of the modulation of energy transfer efficiency at the energy donor site, in a molecular design which has an ICT type metal ion-sensitive chromophore placed as the energy donor in the dyad. Clear advantages emerge compared to the acceptor site modulation: unaltered emission wavelength in the red end of the visible spectrum, while keeping a large Stokes shift and the ratiometric character. © 2009 American Chemical Society.
Open Access
Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development
(Elsevier B.V., 2017) Bayyurt, B.; Tincer, G.; Almacioglu, K.; Alpdundar, E.; Gursel, M.; Gursel, I.
Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine. ï¿½ 2017 Elsevier B.V.
Open Access
Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction
(Public Library of Science, 2017) Gucluler, G.; Adiguzel, E.; Gungor, B.; Kahraman, T.; Gursel, M.; Yilmaz, B.; Gursel, I.
Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. © 2017 Gucluler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Open Access
Near-IR-triggered, remote-controlled release of metal ions: A novel strategy for caged ions
(Wiley-VCH Verlag, 2014) Atilgan, A.; Eçik, E. T.; Guliyev, R.; Uyar, T. B.; Erbas-Cakmak, S.; Akkaya, E. U.
A ligand incorporating a dithioethenyl moiety is cleaved into fragments which have a lower metal-ion affinity upon irradiation with low-energy red/near-IR light. The cleavage is a result of singlet oxygen generation which occurs on excitation of the photosensitizer modules. The method has many tunable factors that could make it a satisfactory caging strategy for metal ions.
Open Access
Novel molecular building blocks based on the boradiazaindacene chromophore: applications in fluorescent metallosupramolecular coordination polymers
(2009) Bozdemir, Ö. A.; Büyükcakir, O.; Akkaya, E. U.
We designed and synthesized novel boradiazaindacene (Bodipy) derivatives that are appropriately functionalized for metal-ion-mediated supramolecular polymerization. Thus, ligands for 2-terpyridyl-, 2,6-terpyridyl-, and bipyridyl-functionalized Bodipy dyes were synthesized through Sonogashira couplings. These fluorescent building blocks are responsive to metal ions in a stoichiometry-dependent manner. Octahedral coordinating metal ions such as Zn II result in polymerization at a stoichiometry corresponding to two terpyridyl ligands to one Zn II ion. However, at increased metal ion concentrations, the dynamic equilibria are re-established in such a way that the monomeric metal complex dominates. The position of equilibria can easily be monitored by 1H NMR and fluorescence spectroscopies. As expected, although open-shell Fe II ions form similar complex structures, these cations quench the fluorescence emission of all four functionalized Bodipy ligands. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Open Access
Selective manipulation of ICT and PET processes in styryl-bodipy derivatives: Applications in molecular logic and fluorescence sensing of metal ions
(2010) Bozdemir, O. A.; Guliyev, R.; Buyukcakir, O.; Selcuk, S.; Kolemen, S.; Gulseren, G.; Nalbantoglu, T.; Boyaci, H.; Akkaya, E. U.
Remarkably versatile chemistry of Bodipy dyes allows the design and straightforward synthesis of multivalent-multitopic derivatives, which, with judicious selection of metal ion-ligand pairs based on known affinities, affords control and manipulation of photoinduced electron transfer and internal charge transfer processes as desired. We have demonstrated that metal ions acting as modulators (or inputs, in digital design parlance) can generate absorbance changes in accordance with the operation of a half-adder. In addition, an AND logic gate in the emission mode was delivered using a different binucleating arrangement of ligands. A molecular equivalent of a three-input AND logic gate was also obtained exploiting differential binding affinities of metal ions for different ligands. The results suggest that different metal ions can be used as nonannihilating inputs, selectively targeting various ligands incorporated within a single fluorophore, and with careful design, diverse photophysical processes can be selectively modulated, resulting in a range of signals, useful in molecular logic design, and offering an enticing potential for multianalyte chemosensors.