https://doi.org/10.15255/KUI.2002.029
Published: Kem. Ind. 53 (2) (2004) 63–70
Paper reference number: KUI-29/2002
Paper type: Review
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Glycoconjugates as Models in Biomedical Studies

I. Jerić and Š. Horvat

Abstract

It is becoming evident that the main outcome of the Human Genome Project is not only identification of human genes, but more important, the conception of proteins and their conjugates being the key structural and functional players in biological systems. The main goal in post-genomic era is to find the most important therapeutic targets for drug discovery, which include understanding of structure and function of all biomolecules involved in biological process. Having in mind complexity and heterogeneity of macromolecules, the demand for suitable model compounds to probe the nature of biological processes is well understandable. Our approach involves glycoconjugates with an ester type of linkage between the C-terminus of the amino acid Tyr (1), or peptides Tyr-Pro (2), Tyr-Pro-Phe (3) and Tyr-Pro-Phe-Val (4), and the C-6 hydroxy group of the D-glucose as model compounds, to study phenomena associated with a complex group of reactions, collectively known as the Maillard reaction. The main issue was to clear up the influence of the structure and the length of the peptide residue on the overall reactivity of studied glycopeptide esters. It is found that changes in the length of glycopeptides with an identical N-terminal part give rise to specific chemical reactions, resulting in the formation of diketopiperazine 11, glycosylamine 12 or keto-sugar derivative 13. In addition, NMR spectroscopy and molecular modelling were used to determine the conformational features of cyclic sugar-peptide adducts 12 and 13, and the obtained results were correlated with the observed chemical behavior. Finally, a small library of glycoconjugates with distinct structural differences was used in mass spectrometric study to establish fragmentation pattern and to find characteristic structures that can be used as markers for identification of complex systems, either naturally occurring or synthetically obtained.

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Keywords

glycopeptide esters, Maillard, NMR spectroscopy, molecular modelling, mass spectrometry