A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme.
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http://dx.doi.org/10.1021/ja907363k | DOI Listing |
Fluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
View Article and Find Full Text PDFBMC Res Notes
January 2025
Department of Anatomy and Neuroscience, Institute of Medicine, University of Tsukuba, 1-1- 1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Objective: Reactivity of microglia, the resident cells of the brain, underlies innate immune mechanisms (e.g., injury repair), and disruption of microglial reactivity has been shown to facilitate psychiatric disorder dysfunctions.
View Article and Find Full Text PDFThe human () gene encodes a plasma membrane protein SLC39A8 (ZIP8) that mediates the specific uptake of the metals Cd, Mn, Zn, Fe, Co, and Se Pathogenic variants within are associated with congenital disorder of glycosylation type 2 (CDG type II) or Leigh-like syndrome. However, numerous mutations of uncertain significance are also linked to different conditions or benign traits. Our study characterized 21 variants and measured their impact on protein localization and intracellular levels of Cd, Zn, and Mn We identified four variants that disrupt protein expression, five variants with high retention in the endoplasmic reticulum, and 12 variants with localization to the plasma membrane.
View Article and Find Full Text PDFLife Sci Alliance
April 2025
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
I'm Not Dead Yet (INDY) functions as a transporter for citrate, a key metabolite in the citric acid cycle, across the plasma membrane. Partial deficiency of INDY extends lifespan, akin to the effects of caloric restriction. In this work, we use cryo-electron microscopy to determine structures of INDY in the presence and absence of citrate and in complex with the well-known inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) at resolutions ranging from 2.
View Article and Find Full Text PDFMol Cell Endocrinol
January 2025
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032, Debrecen, Hungary. Electronic address:
Brown and beige adipocytes express uncoupling protein-1 (UCP1), which is located in the inner mitochondrial membrane and facilitates the dissipation of excess energy as heat. The activation of thermogenic adipocytes is a potential therapeutic target for treating type 2 diabetes mellitus, obesity, and related co-morbidities. Therefore, identifying novel approaches to stimulate the function of these adipocytes is crucial for advancing therapeutic strategies.
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