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A Dual-Fluorescence Molecular "Open Bridge" for Evaluating Gestational Hypoxia and Hypertension under the Stress of
Meihui Hou1, Haipei Chu1,2, Wenmin Hou1
1School of Biological Science and Technology, University of Jinan, 336 West Road of Nan, Xinzhuang 250022, China.
Gestational hypertension is a dangerous condition that is sometimes fatal to the mother and her unborn off-spring. The strong connection between hypertension and hypoxia is emphasized by the currently rampaging SARS-Cov-2, which can induce similar conditions, in which hemolysis and the subsequent oxidative damage may release hemoglobin and tissue factor into the serum. To detect these dangerous proteins normally absent from serum, we mimic the molecular pathology of hypoxia, resulting in a synthesizable molecular machine around which a new bioassay can be designed to simultaneously detect the two proteins in a one-step and reagentless fashion. The "open bridge"-like probe can split into two upon ATP-induced cross-linking of hemoglobin to the probe. The covalently captured hemoglobin can subsequently use its peroxidase-like activity to induce a second cross-coupling between the probe and the tissue factor. A fluorescent probe-target covalent complex is formed, enabling thorough rinsing to minimize nonspecific interference. Finally, using hemoglobin's peroxidase activity to improve sensitivity, the assay has been successfully applied in detecting the two proteins in the periphery serum of pregnant women. These results may promise a near future application of the proposed method for providing an early warning for gestational hypoxia and hypertension, particularly under the stress of SARS-Cov-2.
Gestational hypertension is a dangerous condition that is sometimes fatal to the mother and her unborn off-spring. The strong connection between hypertension and hypoxia is emphasized by the currently rampaging SARS-Cov-2, which can induce similar conditions, in which hemolysis and the subsequent oxidative damage may release hemoglobin and tissue factor into the serum. To detect these dangerous proteins normally absent from serum, we mimic the molecular pathology of hypoxia, resulting in a synthesizable molecular machine around which a new bioassay can be designed to simultaneously detect the two proteins in a one-step and reagentless fashion. The "open bridge"-like probe can split into two upon ATP-induced cross-linking of hemoglobin to the probe. The covalently captured hemoglobin can subsequently use its peroxidase-like activity to induce a second cross-coupling between the probe and the tissue factor. A fluorescent probe-target covalent complex is formed, enabling thorough rinsing to minimize nonspecific interference. Finally, using hemoglobin's peroxidase activity to improve sensitivity, the assay has been successfully applied in detecting the two proteins in the periphery serum of pregnant women. These results may promise a near future application of the proposed method for providing an early warning for gestational hypoxia and hypertension, particularly under the stress of SARS-Cov-2.
