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Biocatalyzed Synthesis of Antidiabetic Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
To improve the ADME properties of pramlidine, a biocatatalyzed glycosylation protocol was described (Kowalczyk et al., 2014) using endo-β-N-acetylglucosaminidases (ENGases), enzymes which all cleave the chitobiose core of N-linked glycans (Fairbanks, 2017), but can be used in a reverse mode to attach N-glycans to substrates containing N-acetylglucosamine (GlcNAc) as an ‘acceptor’ handle. In this reverse action, N-glycan oxazolines are used as activated donors. Hence, these authors reported the synthesis of a variety of pramlintide glycoconjugates in which some Asn residues were modified by attaching a carbohydrate moiety, as depicted in Fig. 11.6. Glycosilated pramlintide derivatives.
The sweet spot for biologics: recent advances in characterization of biotherapeutic glycoproteins
Published in Expert Review of Proteomics, 2018
Róisín O’Flaherty, Irena Trbojević-Akmačić, Gordon Greville, Pauline M. Rudd, Gordan Lauc
Glycosylation of biotherapeutic glycoproteins plays an important role in cellular communication in vivo and can alter function, safety, and efficacy of the drug. It is estimated that more than 50% of human proteins are glycosylated and approximately 90% of these contain N-linked glycans or a combination of N-linked and O-linked glycans [1]. Many of the protein-based biotherapeutics approved or in clinical trials are glycoproteins, including the large class of monoclonal antibodies (mAbs), cytokines and enzyme replacement therapies. mAbs based on immunoglobulin G 1 (IgG1), an antibody for Fc receptor binding are frequently exploited as therapeutic agents, see Figure 1. Human IgG1 antibodies contain two conserved N-glycan sites on the Fc (fragment crystallizable) at Asn 297 on each heavy chain, and up to four additional N-glycan sites on the Fab (fragment antibody binding) [2]. N-glycans contain a common chitobiose core of two N-acetylglucosamine residues (GlcNAc) linked to an asparagine residue on the glycoprotein via an amide bond and extended with a trimannosyl core, see Figure 1. This core structure may be decorated with additional monosaccharide residues such as mannose (Man), GlcNAc, galactose (Gal), fucose (Fuc), bisecting GlcNAc, and sialic acids such as N-acetyl neuraminic acid (NANA) or N-glycolyl neuraminic acid (NGNA). Biosynthesis of eukaryotic N- and O-glycosylation has been extensively described in the literature previously [4,5].
Nanostructured cochleates: a multi-layered platform for cellular transportation of therapeutics
Published in Drug Development and Industrial Pharmacy, 2019
Pravin Shende, Rohan Khair, Ram S. Gaud
The trapping method was used in the preparation of cochleates without using CaCl2 solution. Chitobiose solution was added dropwise in a cyclosporine-loaded liposome suspension [56]. In vitro and in vivo studies showed the release profile of cyclosporine A encapsulated in chitosan-based nanocochleates was much higher because of greater surface area than drug-loaded calcium-based nanocochleates [57].
Synthesis, antiasthmatic, and insecticidal/antifungal activities of allosamidins
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Gangliang Huang, Hualiang Huang
It was indicated that chitobiose and chitotriose thiazolines (24 and 25) were synthesized by traditional method. As above-mentioned, the of allosamidin 1 was synthesized by solid phase method. So, compound 25 was successfully synthesized by the similar approach (Scheme 7)57. Compounds 36 and 39 were used as the corresponding α-trichloroacetimidate donors.