Fine Tuning of the HOMO–LUMO Gap of 6‐(Thiophen‐2‐yl) indolizino[3,2‐<i>c</i>]quinolines and their Self‐Assembly to Form Fluorescent Organic Nanoparticles: Rational Design and Theoretical Calculations

Park, Jaehyun; Lee, Ji Hye; Lim, Bumhee; Lee, Na Keum; Sim, Gyuseok; Ryu, Soojung; Kim, Ikyon; Hwang, Hyonseok; Lee, Jeeyeon

doi:10.1002/cptc.202000099

Cited by 2 publications

(1 citation statement)

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“…Ab initio molecular dynamics (aiMD): DFT is combined with the equations of motions to describe the evolution of nuclei Time-dependent (TD) DFT: employ linear response theory to compute, e.g., optical properties Dyes for FONs with (TD)-DFT [172][173][174] Atomistic Technique: All-Atoms (AAs) or United-Atoms (UAs)…”

Section: Computational and Theoretical Approaches For Modeling Fonsmentioning

confidence: 99%

Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review

et al. 2022

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Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.

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Section: Computational and Theoretical Approaches For Modeling Fonsmentioning

confidence: 99%

Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review

et al. 2022

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Development of PD3 and PD3-B for PDEδ inhibition to modulate KRAS activity

Lee

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Despite extensive efforts over 40 years, few effective KRAS inhibitors have been developed to date, mainly due to the undruggable features of KRAS proteins. In addition to the direct approach to KRAS via covalent inhibition, modulation of the prenyl-binding protein PDEδ that binds with farnesylated KRAS has emerged as an alternative strategy to abrogate KRAS activity. For the verification of new therapeutic strategies, chemical probes with the dual functions of visualisation and pharmacological inhibition against oncogenic proteins are enormously valuable to understand cellular events related to cancer. Here, we report indolizino[3,2-c]quinoline (IQ)-based fluorescent probes ( PD3 and PD3-B ) for PDEδ inhibition. By using the unique fluorescent characteristics of the IQ scaffold, a fluorescence polarisation (FP)-based binding assay identified PD3 as the most effective PDEδ probe among the tested PD analogues, with a low K d value of 0.491 µM and long retention time in the binding site of PDEδ. In particular, a FP-based competition assay using deltarasin verified that PD3 occupies the farnesylation binding site of PDEδ, excluding the possibility that the FP signals resulted from non-specific hydrophobic interactions between the ligand and protein in the assay. We also designed and synthesised PD3-B ( 5 ), an affinity-based probe (ABP) from the PD3 structure, which enabled us to pull down PDEδ from bacterial lysates containing a large number of intrinsic bacterial proteins. Finally, KRAS relocalization was verified in PANC-1 cells by treatment with PD3 , suggesting its potential as an effective probe to target PDEδ.

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Fine Tuning of the HOMO–LUMO Gap of 6‐(Thiophen‐2‐yl) indolizino[3,2‐c]quinolines and their Self‐Assembly to Form Fluorescent Organic Nanoparticles: Rational Design and Theoretical Calculations

Cited by 2 publications

References 54 publications

Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review

Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review

Development of PD3 and PD3-B for PDEδ inhibition to modulate KRAS activity

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