Glycopeptides substrates

Analytical Properties Substrate has 38 chiral centers and 7 aromatic rings surrounding 4 cavities (A, B, C, D), making this the most structurally complex of the macrocyclic glycopeptides substrate has a relative molecular mass of 2066 this phase can be used in normal, reverse, and polar organic phase separations selective for anionic chiral species with polar organic mobile phases, it can be used for a-hydroxy acids, profens, and N-blocked amino acids in normal phase mode, it can be used for imides, hydantoins, and N-blocked amino acids in reverse phase, it can be used for a-hydroxy and halogenated acids, substituted aliphatic acids, profens, N-blocked amino acids, hydantoins, and peptides Reference 47, 48... 

Figure 20 Rapid profiling of glycosyltransferase substrate specificities in vitro using chemical reporters, (a) Azido-ELISA schematic for profiling ppGalNAcT substrate specificities (b) comparative analysis of ppGalNAcT activities with a library of glycopeptide substrates. ...

Owing to flexibility in the substrate, the TycATE was also used to synthesize a variety of novel cyclic structures. Inclusion of a propargylated amino acid into the linear substrate allowed the synthesis of over 247 macrocyclic glycopeptides, where azido-sugars were coupled onto the cyclized alkyne via copper-catalyzed 1,3-dipolar cycloaddition [44] (Figure 13.12). 

Although the limitations of the enzymic reactions lie in the substrate selectivity and in the availability of enzymes and appropriate nucleotide sugar derivatives, further developments in this field will offer an interesting and efficient potential for the synthetic construction of glycopeptides of biological interest. 

Since the natural target of macrocyclic antibiotics is the A-acyl-D-alanyl-D-alanine terminus (see Section 2.1), the early choice of suitable substrates for this kind of CSPs was that of amino acids [45]. However, it turned out that the macrocyclic CSPs were very successful not only in amino acids enantioresolution, but also in the separation of a wide variety of different structures. The early stages of application of macrocyclic antibiotics have been surveyed in the different fields of chromatography [1,2]. A summary of the different categories of chiral compounds separated by HPLC on glycopeptides containing CSPs is reported in Table 2.3. 

Tertiary treatment implemented Genes encoding D-alanine D-alanine ligases with a broad substrate specificity confer inducible resistance to the glycopeptides antibiotics, as vancomycin World Health Organization Wild-type... 

Clark, R.S., Banerjee, S., and Coward, J.K. (1990) Yeast oligosaccharyltrans-ferase glycosylation of peptide substrates and chemical characterization of the glycopeptide product./. Org. Chem. 55, 6275-6285. 

Schultz, M. and Kunz, FI. (1993) Synthetic O-glycopeptides as model substrates for glycosyltransferases. Tetrahedron Asymmetry 4, 1205-1220. 

The enzymatic synthesis of glycopeptides does not require protection of the functional groups of the amino acid side chains and sugar hydroxyls, because of the high stereoselectivity and regioselectivity of proteases. However, the substrate selectivity of these enzymes may limit a wider range of applications. 

Jansson AM, Jensen KJ, Meldal M, Lomako J, Lomako WM, Olsen CE, Bock K, Solid-phase glycopeptide synthesis of tyrosine-glycosylated glycogenin fragments as substrates for glucosylation by glycogenin, J. Chem. Soc. Perkin. Trans., 11001, 1996. 

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