Immune recognition of viral glycoproteins is probably influenced by their glycosylation. Gp120 of HIV-1, for example, consists of 50% carbohydrate and, together with many other glycoproteins, contains glycosylation sites within or close to both B- and T-cell determinants. It is highly likely that the glycosylation affects the recognition of both B- and T-cells by stabilizing the structures recognized. Immunogenic effects of carbohydrate moieties attached to protein fragments are difficult to address unless a method of preparing the appropriate tools is at hand. This proposal is focused on the synthesis of these tools (glycopeptides) and the assessment of glycosylation effects on the conformation of peptides involved in immune recognition. We propose to extend the solid-phase synthetic method, which we used to synthesize glycopeptides carrying Asn(GIcNAc) residue, to longer and branched carbohydrate chains with O-glycosydic bonds between the sugar moieties. These structures mimic the naturally occurring ones. We will use physical-chemical methods such as CD and NMR to measure the influence of incorporation of different carbohydrate chains to specific and non- specific positions on the conformation of epitopic peptides. The conformation data obtained will be compared with recognition of differentially glycosylated and parent non-glycosylated peptides by T- and B-cells. These studies will give clues to the minimal criteria of sequence and conformation necessary for glycopeptide structures to stimulate T cells and elicit neutralizing antibody production against viral glycoproteins.

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National Institute of General Medical Sciences (NIGMS)
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Wistar Institute
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Cudic, M; Otvos Jr, L (2002) Intracellular targets of antibacterial peptides. Curr Drug Targets 3:101-6
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