Subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs) are common brain lesions found in patients with tuberous sclerosis complex (TSC). These brain lesions present a mixed glioneuronal phenotype and have been hypothesized to originate from neural stem cells. However, this hypothesis has not been tested empirically. Here, we report that loss of Tsc1 in mouse subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) results in formation of SEN-and SEGA-like structural abnormalities in the lateral ventricle, the consequence of abnormal migration of NSPCs following Tsc1 loss.
This paper investigates the transesterification of methyl 3-mercaptopropionate (MP-SH) with tetraethylene glycol (TEG) and poly(ethylene glycol)s (PEG)s catalyzed by Candida antarctica Lipase B (CALB) without the use of solvent (in bulk). The progress of the reactions was monitored by 1H-NMR spectroscopy. We found that the reactions proceeded in a step-wise manner, first producing monothiols. TEG-monothiol was obtained in 15 min, while conversion to dithiol took 8 h. Monothiols from PEGs with Mn = 1000 and 2050 g/mol were obtained in 8 and 16 h, respectively. MALDI-ToF mass spectrometry verified the absence of dithiols. The synthesis of dithiols required additional fresh CALB and MP-SH. The structure of the products was confirmed by 1H-NMR and 13C-NMR spectroscopy. Enzyme catalysis was found to be a powerful tool to effectively synthesize thiol-functionalized TEGs and PEGs.
This paper reports the first “Click” Michael addition catalyzed by Candida antarctica lipase B (CALB) between fluorescein o‐acrylate and thiol‐functionalized poly(ethylene glycol)s (HS‐PEG‐SH, Mn = 1200 g mol−1, Đ = 1.14, and Mn = 2200 g mol−1, Đ = 1.09). The progress of the reactions is monitored with 1H‐NMR spectroscopy. In the absence of CALB, the reaction does not go to completion even after 18 h but completes in less than 2 min when CALB is added. Similarly, the reaction with HS‐PEG‐SH having Mn = 2200 g mol−1 and Đ = 1.09 completes in less than 2 min by CALB catalysis. The structures of the products are also confirmed by 13C‐NMR. This enzyme‐catalyzed “Click” Michael addition is found to be a powerful tool to synthesize fluorescein‐based polymeric conjugates for a wide variety of applications.
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