User:Alib2022/Glycoprotein
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Article Draft[edit]
Glycoproteins are proteins that are enzymatically bonded to oligosaccharides.[1][2] Though there are different types of glycoproteins, the most common are N-linked and O-linked glycoproteins.[3] These two types of glycoproteins each have structural differences and are examples of how different glycoproteins can be structurally. Glycoproteins vary greatly in composition, making many different compounds such as antibodies or hormones.[1] Due to the array of functions within the body, interest in glycoprotein research medical use has increased.[4] There are now several methods to synthesize glycoproteins, including recombination and glycosylation of proteins.[4]
Structure[edit]
The critical structural element of all glycoproteins is having oligosaccharides bonded covalently to a protein.[1] There are 10 common monosaccharides in mammalian glycans including: glucose (Glc), fucose (Fuc), xylose (Xyl), mannose (Man), galactose (Gal), N-acetylglucosamine (GlcNAc), glucuronic acid (GlcA), iduronic acid (IdoA), N-acetylgalactosamine (GalNAc), sialic acid, and 5-N-acetylneuraminic acid (Neu5Ac).[2] These glycans link themselves to specific areas of the protein amino acid chain.
The two most common linkages in glycoproteins are N-linked and O-linked glycoproteins.[3] An N-linked glycoprotein has glycan bonds to the nitrogen containing an Asparagine amino acid within the protein sequence.[1] An O-linked glycoprotein is where the sugar is bonded to an oxygen atom of a Serine or Threonine amino acid in the protein.[1]
Glycoprotein size and composition can vary largely, with carbohydrate composition ranges from 1% to 70% of the total mass of the glycoprotein.[1] Within the cell, they appear in the blood, the extracellular matrix, or on the outer surface of the plasma membrane, and make up a large portion of the proteins secreted by eukaryotic cells.[1] They are very broad in their applications and can function as a variety of chemicals from antibodies to hormones.[1]
Glycomics[edit]
Glycomis is the study of the carbohydrate components of cells.[1] Though not exclusive to glycoproteins, it can reveal more information about different glycoproteins and their structure.[1] One of the purposes of this field of study is to determine which proteins are glycosylated and where in the amino acid sequence the glycosylation occurs.[1] Historically, mass spectrometry has been used to identify the structure of glycoproteins and characterize the carbohydrate chains attached.[1][5]
Applications[edit]
*to be added to another section of the article that is already written*
The unique interaction between the oligosaccharide chains have different applications. First, it aids in quality control by identifying misfolded proteins.[1] The oligosaccharide chains also change the solubility and polarity of the proteins that they are bonded to.[1] For example, if the oligosaccharide chains are negatively charged, with enough density around the protein, they can repulse proteolytic enzymes away from the bonded protein.[1] The diversity in interactions lends itself to different types of glycoproteins with different structures and functions.[4]
P-glycoproteins are critical for antitumor research due to its ability block the effects of antitumor drugs.[1][6] P-glycoprotein, or multidrug transporter (MDR1), is a type of ABC transporter that transports compounds out of cells.[1] This transportation of compounds out of cells includes drugs made to be delivered to the cell, causing a decrease in drug effectiveness.[1] Therefore, being able to inhibit this behavior would decrease P-glycoprotein interference in drug delivery, making this an important topic in drug discovery.[1] For example, P-Glycoprotein causes a decrease in anti-cancer drug accumulation within tumor cells, limiting the effectiveness of chemotherapies used to treat cancer.[6]
Synthesis[edit]
The glycosylation of proteins has an array of different applications from influencing cell to cell communication to changing the thermal stability and the folding of proteins.[1][7] Due to the unique abilities of glycoproteins, they can be used in many therapies.[7] By understanding glycoproteins and their synthesis, they can be made to treat cancer, Crohn's Disease, high cholesterol, and more.[2]
The process of glycosylation (binding a carbohydrate to a protein) is a post-translational modification, meaning it happens after the production of the protein.[2] Glycosylation is a process that roughly half of all human proteins undergo and heavily influences the properties and functions of the protein.[2] Within the cell, glycosylation occurs in the endoplasmic reticulum.[2]
Recombination[edit]
There are several techniques for the assembly of glycoproteins. One technique utilizes recombination.[2] The first consideration for this method is the choice of host, as there are many different factors that can influence the success of glycoprotein recombination such as cost, the host environment, the efficacy of the process, and other considerations.[2] Some examples of host cells include E. coli, yeast, plant cells, insect cells, and mammalian cells.[2] Of these options, mammalian cells are the most common because their use does not face the same challenges that other host cells do such as different glycan structures, shorter half life, and potential unwanted immune responses in humans.[2] Of mammalian cells, the most common cell line used for recombinant glycoprotein production is the Chinese hamster ovary line.[2] However, as technologies develop, the most promising cell lines for recombinant glycoprotein production are human cell lines.[2]
Glycosylation[edit]
The formation of the link between the glycan and the protein is key element of the synthesis of glycoproteins.[4] The most common method of glycosylation of N-linked glycoproteins is through the reaction between a protected glycan and a protected Asparagine.[4] Similarly, an O-linked glycoprotein can be formed through the addition of a glycosyl donor with a protected Serine or Threonine.[4] These two methods are examples of natural linkage.[4] However, there are also methods of unnatural linkages.[4] Some methods include ligation and a reaction between a serine-derived sulfamidate and thiohexoses in water.[4] Once this linkage is complete, the amino acid sequence can be expanded upon using solid-phase peptide synthesis.[4]
See Also[edit]
References[edit]
- ^ a b c d e f g h i j k l m n o p q r s t Verfasser., Nelson, David L. 1942- (2013). Lehninger principles of biochemistry, sixth edition. ISBN 978-1-319-38149-3. OCLC 1249676451.
{{cite book}}:|last=has generic name (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) - ^ a b c d e f g h i j k l "Recombinant Glycoprotein Production | SpringerLink" (PDF). doi:10.1007/978-1-4939-7312-5.pdf.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b Herausgeber, Picanço e Castro, Virginia Herausgeber Swiech, Kamilla. Recombinant Glycoprotein Production Methods and Protocols. ISBN 978-1-4939-7312-5. OCLC 1005519572.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ a b c d e f g h i j Gamblin, David P.; Scanlan, Eoin M.; Davis, Benjamin G. (2008-12-18). "Glycoprotein Synthesis: An Update". Chemical Reviews. 109 (1): 131–163. doi:10.1021/cr078291i. ISSN 0009-2665.
- ^ Dell, Anne; Morris, Howard R. (2001-03-23). "Glycoprotein Structure Determination by Mass Spectrometry". Science. 291 (5512): 2351–2356. doi:10.1126/science.1058890. ISSN 0036-8075.
- ^ a b Ambudkar, Suresh V.; Kimchi-Sarfaty, Chava; Sauna, Zuben E.; Gottesman, Michael M. (2003-10-23). "P-glycoprotein: from genomics to mechanism". Oncogene. 22 (47): 7468–7485. doi:10.1038/sj.onc.1206948. ISSN 1476-5594.
- ^ a b Davis, Benjamin G. (2002-01-29). "Synthesis of Glycoproteins". Chemical Reviews. 102 (2): 579–602. doi:10.1021/cr0004310. ISSN 0009-2665.