The post-translational modification of histones plays an important role in gene expression. We report herein on a method for synthesizing such modified histones by ligating chemically prepared N-terminal peptides and C-terminal recombinant peptide building blocks. Based on their chemical synthesis, core histones can be categorized as two types; histones H2A, H2B and H4 which contain no Cys residues, and histone H3 which contains a Cys residue(s) in the C-terminal region. A combination of native chemical ligation and desulphurization can be simply used to prepare histones without Cys residues. For the synthesis of histone H3, the endogenous Cys residue(s) must be selectively protected, while keeping the N-terminal Cys residue of the C-terminal building block that is introduced for purposes of chemical ligation unprotected.
IPR welcomed a group of members from the College of Life Science, National Tsing Hua University on July 28, 2015, to discuss the
establishment of collaborative research agreements between the two.
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The chemical synthesis of human interleukin-2 (IL-2) , having a core 1 sugar, by a ligation method is reported. Although IL-2 is a globular glycoprotein, its C-terminal region, in particular (99-133), is extremely insoluble when synthesized by solid-phase method. To overcome this problem, the side-chain carboxylic acid of the Glu residues was protected by a picolyl ester, thus reversing its polarity from negative to positive. This reverse polarity protection significantly increased the isoelectric point of the peptide segment and made it positive under acidic conditions and facilitated the purification. An efficient method to prepare the prolyl peptide thioester required for the synthesis of the (28-65) segment was also developed. These efforts resulted in the total synthesis of the glycosylated IL-2 having full biological activity.
KEYWORDS: Prdm13; amacrine cell; interneuron; retina; subtype specification; visual function
Osaka University and Nippi Inc., a Japanese biotech company having an expertise in collagen and collagen-related products, succeeded in manufacturing laminin-511 E8 fragment, a very potent cell-adhesive substrates for cultivation of human pluripotent stem cells, in accordance with GMP (good manufacturing practice). The laminin fragment, commercialized from Nippi under the trade name of “iMatrix-511 MG”, is suitable for production of clinical-grade human iPS cells and other stem cells in cell transplantation therapy. The new product will be commercially available in June 2015. iMatrix-511 GM will accelerate the production of a wide variety of pluripotent stem cells, particularly iPS cells, to be used in regenerative medicine.
- Protein 4.1G is essential for the arrangement of correct retinal synapse location
- 4.1G contributes to membrane-trafficking system mediated by neuronal AP3
- Retinal synaptic location is important for establishing normal visual acuity
- Normal membrane trafficking is essential for synaptic integrity maintenance
SorLA is a neuronal sorting receptor considered to be a major risk factor for Alzheimer’s disease. We have recently reported that it directs lysosomal targeting of nascent neurotoxic amyloid-β (Aβ) peptides by directly binding Aβ. Here, we determined the crystal structure of the human sorLA domain responsible for Aβ capture, Vps10p, in an unbound state and in complex with two ligands. Vps10p assumes a ten-bladed β-propeller fold with a large tunnel at the center. An internal ligand derived from the sorLA propeptide bound inside the tunnel to extend the β-sheet of one of the propeller blades. The structure of the sorLA Vps10p-Aβ complex revealed that the same site is used. Peptides are recognized by sorLA Vps10p in redundant modes without strict dependence on a particular amino acid sequence, thus suggesting a broad specificity toward peptides with a propensity for β-sheet formation.
IPR concluded an academic exchange agreement with College of Pharmacy, Seoul National University on January 5, 2015. The agreement aims to enhance academic exchange and research collaboration among students and researchers between our institutes, with common goal to advance scientific research in Asia together.
IPR concluded an academic exchange agreement with College of Physical and Mathematical Science, Research School of Chemistry, the Australian National University on November 20, 2014. The agreement aims to enhance academic exchange and research collaboration among students and researchers between our institutes, with common goal to advance scientific research in Asia and Oceania together.