Glycopeptides are

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

s that contain

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

moieties ( glycans) covalently attached to the

side chain In organic chemistry and biochemistry, a side chain is a substituent, chemical group that is attached to a core part of the molecule called the "main chain" or backbone chain, backbone. The side chain is a hydrocarbon branching element of a mo ...

s of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

residues that constitute the peptide. Over the past few decades it has been recognised that glycans on cell surface (attached to membrane proteins or

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

s) and those bound to proteins ( glycoproteins) play a critical role in biology. For example, these constructs have been shown to play important roles in

fertilization Fertilisation or fertilization (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give ...

, the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

brain development The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special sens ...

, the

endocrine system The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant Organ (biology), organs. In vertebrat ...

, and

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

. The synthesis of glycopeptides provides biological probes for researchers to elucidate glycan function in nature and products that have useful therapeutic and biotechnological applications.

Glycopeptide linkage variety

''N''-Linked glycans

''N''-Linked glycans derive their name from the fact that the glycan is attached to an asparagine (Asn, N) residue, and are amongst the most common linkages found in nature. Although the majority of N-linked glycans take the form GlcNAc-β-Asn other less common structural linkages such as GlcNac-α-Asn and Glc-Asn have been observed. In addition to their function in protein folding and cellular attachment, the N-liked glycans of a protein can modulate the protein's function, in some cases acting as an on-off switch.

''O''-Linked glycans

''O''-Linked glycans are formed by a linkage between an

hydroxyl side chain (usually from serine or threonine) with the glycan. The majority of ''O''-linked glycans take the form GlcNac-β-Ser/Thr or GalNac-α-Ser/Thr.

''C''-Linked glycans

Of the three linkages the least common and least understood are ''C''-linked glycans. The C-linkage refers to the covalent attachment of mannose to a tryptophan residue. An example of a C-linked glycan is α-mannosyl tryptophan.

Glycopeptide synthesis

Several methods have been reported in the literature for the synthesis of glycopeptides. Of these methods the most common strategies are listed below.

Solid phase peptide synthesis

Within solid phase peptide synthesis (SPPS) there exist two strategies for the synthesis of glycopeptides, linear and convergent assembly. Linear assembly relies on the synthesis of building blocks and then the use of SPPS to attach the building block together. An outline of this approach is illustrated below. Several methods exist for the synthesis of

monosaccharide Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. Chemically, monosaccharides are polyhy ...

amino acid building block as illustrated below. Provided the monosaccharide amino acid building block is stable to peptide coupling conditions, amine deprotection conditions and resin cleavage. Linear assembly remains a popular strategy for the synthesis of glycopeptides with many examples in the literature. In the convergent assembly strategy a peptide chain and glycan residue are first synthesis separately. Then the glycan is glycosylated onto a specific residue of the peptide chain. This approach is not as popular as the linear strategy due to the poor reaction yields in the

glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

step. Another strategy to produce glycopeptide libraries is using Glyco-SPOT synthesis technique. The technique extends the existing method of SPOT synthesis. In this method, libraries of glycopeptides are produced on a cellulose surface (e.g. filter paper) which acts as the solid phase. The glycopeptides are produced by spotting FMOC protected amino acids allowing the synthesis to be performed at microgram (nanomole) scale using very small amounts of glycoamino acids. The scale of this technique can be an advantage for creating libraries for screening by using less amounts of glycoamino acids per peptide. However to produce larger quantities of glycopeptides traditional resin-based solid phase techniques would be better.

Native chemical ligation

Native chemical ligation (NCL) is a convergent synthetic strategy based on the linear coupling of glycopeptide fragments. This technique makes use of the chemoselective reaction between a N-terminal cysteine residue on one peptide fragment with a thio-ester on the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

of the other peptide fragment as illustrated below. Unlike standard SPPS (which is limited to 50 amino acid residue) NCL allows the construction of large glycopeptides. However the strategy is limited by the fact that it requires a cysteine residue at N-terminus, an amino acid residue that is rare in nature. However this problem has partly been address by the selective desulfurization of the cysteine residue to an alanine.

References

External links

* {{Glycoproteins