Screening of Glycopeptide Libraries

As of this writing, there are presently only two examples of successful synthesis of glycopeptide libraries in the literature, and these have been generated using PEG-based resins (PEGA and POEPOP), thus enabling rapid solid phase screening of the library (see Sections 14.8 and 14.7.2). 

An important requirement for the successful application of the combinatorial library approach to the drug discovery process, is the ability to utilize the library in high-throughput screening (HTS) procedures. HTS screening of glycopeptide... 

Here, we present an overview of the aspects of the design, synthesis, analysis, and screening of combinatorial solid-phase glycopeptide libraries as compared to parallel glycopeptide arrays. 

Figure 14.6 Representative mass spectrum showing ladder of a bisglycosylated glycopeptide obtained from screening of a glycopeptide library for the mannose binding protein. The nonanoic acid (Non) and tridecanoic acid (Tri) encode for Ser(Man) (Sm) and Asn(Man) (Nm), respectively.

Figure 14.8 (A) Screening of a glycopeptide library using a fluorescent-labeled lectin and ligands bound to PEGA beads. The acbve compounds are analysed by mass spectrometry. (B) FITC-labeled lectin binding to resin bound mannose could be inhibited by soluble glycopeptides obtained from library screen. Percent inhibition was quantified by recording of lectin fluorescence. Only every second well of the microtiter plate was used and nonfluorescent beads indicated good inhibitors.44...

St. Hilaire PM, Lowary TL, Meldal M, Bock K, Oligosaccharide mimetics obtained by novel, rapid screening of carboxylic acid encoded glycopeptide libraries, J. Am. Chem. Soc., 120 13312-13320, 1998. 

Hilaire, P.M.St. Lowary, T.L. Meldal,M. Bock, K. OligosaccharideMimetics Obtained by Novel, Rapid Screening of Carboxylic Acid Encoded Glycopeptide Libraries, 7. Am. Chem. Soc. 120, 13312-13320 (1998). 

Figure 8.6. Representative mass spectra showing the Madder of a bis-glycosylated glycopeptide obtained from screening of the deprotected glycopeptide library. The phenylpropionic acid (Ppa) and lauric acid (Lau) encode for Asn(GlcNAc) and Thr(Man), respectively.

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