Rational Design of Bioavailable Photosensitizers for Manipulation and Imaging of Biological Systems.
Ontology highlight
ABSTRACT:
SUBMITTER: Binns TC
PROVIDER: S-EPMC7483975 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The modulation of the photophysical properties of a series of recently synthetized oxobacteriochlorins with the introduction of heavy atoms in the macrocycles, was investigated at density functional level of theory and by means of the time-dependent TDDFT formulation. Absorption frequencies, singlet-triplet energy gaps and spin-orbit coupling (SOC) constants values were computed for all the investigated compounds. Results show how the sulfur- selenium- and iodine-substituted compounds possess improved properties that make them suitable for application in photodynamic therapy (PDT).
| S-EPMC6514987 | biostudies-literature
Project description:Enhancing the oral bioavailability of peptide drug leads is a major challenge in drug design. As such, methods to address this challenge are highly sought after by the pharmaceutical industry. Here, we propose a strategy to identify appropriate amides for N-methylation using temperature coefficients measured by NMR to identify exposed amides in cyclic peptides. N-methylation effectively caps these amides, modifying the overall solvation properties of the peptides and making them more membrane permeable. The approach for identifying sites for N-methylation is a rapid alternative to the elucidation of 3D structures of peptide drug leads, which has been a commonly used structure-guided approach in the past. Five leucine-rich peptide scaffolds are reported with selectively designed N-methylated derivatives. In vitro membrane permeability was assessed by parallel artificial membrane permeability assay and Caco-2 assay. The most promising N-methylated peptide was then tested in vivo. Here we report a novel peptide (15), which displayed an oral bioavailability of 33% in a rat model, thus validating the design approach. We show that this approach can also be used to explain the notable increase in oral bioavailability of a somatostatin analog.
| S-EPMC4267368 | biostudies-literature
Project description:The precision and repeatability of in vivo biological studies is predicated upon methods for isolating a targeted subsystem from external sources of noise and variability. However, in many experimental frameworks, this is made challenging by nonstatic environments during host cell growth, as well as variability introduced by manual sampling and measurement protocols. To address these challenges, we developed Chi.Bio, a parallelised open-source platform that represents a new experimental paradigm in which all measurement and control actions can be applied to a bulk culture in situ. In addition to continuous-culturing capabilities, it incorporates tunable light outputs, spectrometry, and advanced automation features. We demonstrate its application to studies of cell growth and biofilm formation, automated in silico control of optogenetic systems, and readout of multiple orthogonal fluorescent proteins in situ. By integrating precise measurement and actuation hardware into a single low-cost platform, Chi.Bio facilitates novel experimental methods for synthetic, systems, and evolutionary biology and broadens access to cutting-edge research capabilities.
| S-EPMC7419009 | biostudies-literature
Project description:Here we introduce a new design framework for synthetic biology that exploits the advantages of Bayesian model selection. We will argue that the difference between inference and design is that in the former we try to reconstruct the system that has given rise to the data that we observe, whereas in the latter, we seek to construct the system that produces the data that we would like to observe, i.e., the desired behavior. Our approach allows us to exploit methods from Bayesian statistics, including efficient exploration of models spaces and high-dimensional parameter spaces, and the ability to rank models with respect to their ability to generate certain types of data. Bayesian model selection furthermore automatically strikes a balance between complexity and (predictive or explanatory) performance of mathematical models. To deal with the complexities of molecular systems we employ an approximate Bayesian computation scheme which only requires us to simulate from different competing models to arrive at rational criteria for choosing between them. We illustrate the advantages resulting from combining the design and modeling (or in silico prototyping) stages currently seen as separate in synthetic biology by reference to deterministic and stochastic model systems exhibiting adaptive and switch-like behavior, as well as bacterial two-component signaling systems.
| S-EPMC3174594 | biostudies-literature
Project description:Fluorescent small molecules are powerful tools for visualizing biological events, embodying an essential facet of chemical biology. Since the discovery of the first organic fluorophore, quinine, in 1845, both synthetic and theoretical efforts have endeavored to "modulate" fluorescent compounds. An advantage of synthetic dyes is the ability to employ modern organic chemistry strategies to tailor chemical structures and thereby rationally tune photophysical properties and functionality of the fluorophore. This review explores general factors affecting fluorophore excitation and emission spectra, molar absorption, Stokes shift, and quantum efficiency; and provides guidelines for chemist to create novel probes. Structure-property relationships concerning the substituents are discussed in detail with examples for several dye families. We also present a survey of functional probes based on PeT, FRET, and environmental or photo-sensitivity, focusing on representative recent work in each category. We believe that a full understanding of dyes with diverse chemical moieties enables the rational design of probes for the precise interrogation of biochemical and biological phenomena.
| S-EPMC7453994 | biostudies-literature
Project description:The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered.
| S-EPMC5043446 | biostudies-literature
Project description:Current treatments have limited effectiveness in treating tumors. The combination of multiple drugs or treatment strategies is widely studied to improve therapeutic effect and reduce adverse effects of cancer therapy. The codelivery system is the key to realize combined therapies. It is necessary to design and construct different codelivery systems in accordance with the variable structures and properties of cargoes and vectors. This review presented the typical design considerations about codelivery vectors for cancer therapy and described the current state of codelivery systems from two aspects: different types of vectors and collaborative treatment strategies. The commonly used loading methods of cargoes into the vectors, including physical and chemical processes, are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of codelivery systems.
| S-EPMC7264083 | biostudies-literature
Project description:The automated design of imaging systems involving no or minimal human effort has always been the expectation of scientists, researchers and optical engineers. In addition, it is challenging to choose an appropriate starting point for an optical system design. In this paper, we present a novel design framework based on a point-by-point design process that can automatically obtain high-performance freeform systems. This framework only requires a combination of planes as the input based on the configuration requirements or the prior knowledge of designers. This point-by-point design framework is different from the decades-long tradition of optimizing surface coefficients. Compared with the traditional design method, whereby the selection of the starting point and the optimization process are independent of each other and require extensive amount of human effort, there are no obvious differences between these two processes in our design framework, and the entire design process is mostly automated. This automated design process significantly reduces the amount of human effort required and does not rely on advanced design skills and experience. To demonstrate the feasibility of the proposed design framework, we successfully designed two high-performance systems as examples. This point-by-point design framework opens up new possibilities for automated optical design and can be used to develop automated optical design in the areas of remote sensing, telescopy, microscopy, spectroscopy, virtual reality and augmented reality.
| S-EPMC6061905 | biostudies-other
Project description:Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 24h by in-vivo intramuscularly administration of R848, SMIP-7.7, SMIP-7.8 and 4%DMSO controls. Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 6h by in-vivo intramuscularly administration of R848 and SMIP-7.2 in 1% DMSO, and SMIP-7.10 and SMIP-7.10+alum in Buffer.
2015-11-02 | E-MTAB-2948 | biostudies-arrayexpress
Project description:Chemiluminescence (CL) functionalized materials have found tremendous value in developing CL assays for clinical assays and point-of-care tests. To date, the design and optimization of these materials have mainly relied on conventional trial-and-error procedures in which the ensemble performance is evaluated using conditional experiments. Here we have built an optical microscope to acquire the CL emission from single magnetic-polymer hybrid microbeads functionalized with luminol analogues, and to access the CL kinetics of each individual particle. It was incidentally found that a minor subpopulation of microbeads exhibited intense and delayed CL emission while the majority showed transient and weak emission. Structural characterization of the very same individual particles uncovered that the amorphous multi-core microstructures were responsible for the enhanced encapsulation efficiency and optimized CL reaction kinetics. Guided by this knowledge stemming from single particle CL imaging, the synthesis procedure was rationally optimized to enrich the portion of microbeads with better CL performance, which was validated by both single particle imaging and the significantly improved analytical performance at the ensemble level. The present work not only demonstrates the CL imaging and CL kinetics curve of single microbeads for the first time, but also sets a clear example showing the capability of single particle studies to investigate the structure-activity relationship in a bottom-up manner and to help the rational design of ensemble materials with improved performance.
| S-EPMC6553381 | biostudies-literature