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12 pages, 3150 KiB

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Interaction of Aggregated Cationic Porphyrins with Human Serum Albumin

by Mario Samperi, Serena Vittorio, Laura De Luca, Andrea Romeo and Luigi Monsù Scolaro

Int. J. Mol. Sci. 2023, 24(3), 2099; https://doi.org/10.3390/ijms24032099 - 20 Jan 2023

Cited by 6 | Viewed by 2110

The interaction of an equilibrium mixture of monomeric and aggregated cationic trans-5,15-bis(N-methylpyridinium-4-yl)-10,15-bis-diphenylporphine (t-H₂Pagg) chloride salt with human serum albumin (HSA) has been investigated through UV/Vis absorption, fluorescence emission, circular dichroism and resonant light scattering techniques. The spectroscopic evidence reveals that both the monomeric t-H₂Pagg and its aggregates bind instantaneously to HSA, leading to the formation of a tight adduct in which the porphyrin is encapsulated within the protein scaffold (S₄₃₀) and to clusters of aggregated porphyrins in electrostatic interaction with the charged biomolecules. These latter species eventually interconvert into the final S₄₃₀ species following pseudo-first-order kinetics. Molecular docking simulations have been performed to get some insights into the nature of the final adduct. Analogously to hemin bound to HSA, the obtained model supports favorable interactions of the porphyrin in the same 1B subdomain of the protein. Hydrophobic and van der Waals energy terms are the main contributions to the calculated ΔG_bind value of −117.24 kcal/mol. Full article

(This article belongs to the Special Issue Porphyrin and Biomolecules: A Long-Lasting Friendship)

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14 pages, 3814 KiB

Open AccessArticle

Molecular Mechanism of Action of RORγt Agonists and Inverse Agonists: Insights from Molecular Dynamics Simulation

by Nannan Sun, Congmin Yuan, Xiaojun Ma, Yonghui Wang, Xianfeng Gu and Wei Fu

Molecules 2018, 23(12), 3181; https://doi.org/10.3390/molecules23123181 - 3 Dec 2018

Cited by 19 | Viewed by 6986

Abstract

As an attractive drug-target, retinoic acid receptor-related orphan receptor-gamma-t (RORγt) has been employed widely to develop clinically relevant small molecular modulators as potent therapy for autoimmune disease and cancer, but its molecular mechanism of action (MOA) remains unclear. In the present study, we designed and discovered two novel RORγt ligands that are similar in structure, but different in efficacy. Using fluorescence resonance energy transfer (FRET) assay, compound 1 was identified as an agonist with an EC₅₀ of 3.7 μM (max. act.: 78%), while compound 2 as an inverse agonist with an IC₅₀ value of 2.0 μM (max. inh.: 61%). We performed molecular dynamics (MD) simulations, and elucidated the MOA of RORγt agonist and inverse agonist. Through the analyses of our MD results, we found that, after RORγt is bound with the agonist 1, the side chain of Trp317 stays in the gauche- conformation, and thus helps to form the hydrogen bond, His479-Trp502, and a large hydrophobic network among H11, H11′, and H12. All these interactions stabilize the H12, and helps the receptor recruit the coactivator. When the RORγt is bound with the inverse agonist 2, the side chain of Trp317 is forced to adopt the trans conformation, and these presumed interactions are partially destroyed. Taken together, the critical role of residue Trp317 could be viewed as the driving force for the activation of RORγt. Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Symposium for Chinese Medicinal Chemists 2018)

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11 pages, 3168 KiB

Open AccessArticle

Detection of Thrombin Based on Fluorescence Energy Transfer between Semiconducting Polymer Dots and BHQ-Labelled Aptamers

by Yizhang Liu, Xuekai Jiang, Wenfeng Cao, Junyong Sun and Feng Gao

Sensors 2018, 18(2), 589; https://doi.org/10.3390/s18020589 - 14 Feb 2018

Cited by 17 | Viewed by 6002

Abstract

Carboxyl-functionalized semiconducting polymer dots (Pdots) were synthesized as an energy donor by the nanoprecipitation method. A black hole quenching dye (BHQ-labelled thrombin aptamers) was used as the energy acceptor, and fluorescence resonance energy transfer between the aptamers and Pdots was used for fluorescence quenching of the Pdots. The addition of thrombin restored the fluorescence intensity. Under the optimized experimental conditions, the fluorescence of the system was restored to the maximum when the concentration of thrombin reached 130 nM, with a linear range of 0–50 nM (R² = 0.990) and a detection limit of 0.33 nM. This sensor was less disturbed by impurities, showing good specificity and signal response to thrombin, with good application in actual samples. The detection of human serum showed good linearity in the range of 0–30 nM (R² = 0.997), with a detection limit of 0.56 nM and a recovery rate of 96.2–104.1%, indicating that this fluorescence sensor can be used for the detection of thrombin content in human serum. Full article

(This article belongs to the Special Issue Semiconductor Materials on Biosensors Application)

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