The total chemical synthesis of a Forssman antigen analog is described. The pentasaccharide contains a functionalized tether which should facilitate future conjugation with immunogenic proteins. We found that the total synthesis can be efficiently achieved by following a convergent 2+3 strategy, and using N-Troc protected GalNAc thioglycoside as a donor.
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http://dx.doi.org/10.1016/j.carres.2011.09.015 | DOI Listing |
Carbohydr Res
December 2024
M. M. Shemyakin-Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 117997, Moscow, Russian Federation. Electronic address:
A total chemical synthesis of spacer-armed Forssman pentasaccharide is reported. The choice of the 2(donor) + 3(acceptor) block scheme, the optimal combination of a limited number of simple protecting groups and the sequence of deprotection steps allowed to achieve the high yield and stereoselectivity of glycosylation and to avoid losses during deprotection. The target pentasaccharide was obtained in a 10-mg scale.
View Article and Find Full Text PDFPLoS Genet
October 2024
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability and endocrine disorder caused by pathogenic variants of plant homeodomain finger gene 6 (PHF6). An understanding of the role of PHF6 in vivo in the development of the mammalian nervous system is required to advance our knowledge of how PHF6 mutations cause BFLS. Here, we show that PHF6 protein levels are greatly reduced in cells derived from a subset of patients with BFLS.
View Article and Find Full Text PDFAPMIS
January 2025
Department of Veterinary and Animal Science, University of Copenhagen, Copenhagen, Denmark.
Forssman was a Swedish pathologist and microbiologist who, in the 1920s and 1930s conducted a long series of experiments that led to unique insights into surface antigens of blood cells, as well as added to the discrimination of toxins produced by staphylococci that lyse red blood cells. This review takes offset in the studies published by Forssman in APMIS addressing the hemolytic properties of staphylococcal toxins displayed against erythrocytes of animal and human origin. In light of current knowledge, we will discuss the insights we now have and how they may pave the way for curing infections with pathogenic staphylococci, including Staphylococcus aureus.
View Article and Find Full Text PDFHum Genet
June 2024
Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm).
View Article and Find Full Text PDFEMBO Rep
March 2024
Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
The plant homeodomain zinc-finger protein, PHF6, is a transcriptional regulator, and PHF6 germline mutations cause the X-linked intellectual disability (XLID) Börjeson-Forssman-Lehmann syndrome (BFLS). The mechanisms by which PHF6 regulates transcription and how its mutations cause BFLS remain poorly characterized. Here, we show genome-wide binding of PHF6 in the developing cortex in the vicinity of genes involved in central nervous system development and neurogenesis.
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