Synthesis and CD studies of an 88-residue peptide containing the main receptor binding site of HTLV-I SU-glycoprotein

Abstract

Essential HTLV-1 biological functions, like host-cell receptor recognition, depend on the structural motives on the surface glycoprotein gp46. We defined a peptide of 88 amino acids [Arg147-Leu234] corresponding to the central part of the protein sequence, where major neutralizing epitopes are localized. After evaluating the feasibility of its chemical synthesis, the chosen sequence was realized using the stepwise solid-phase methodology. Multiple chromatographic purification steps were required to obtain a sample suitable for structural analysis. Correct folding was supported by strong binding of monooclonal antibodies, recognizing known exposed immunodominant regions. Circular dichroism studies confirmed a non-random conformation of at least 70-80% of the synthetic peptide. Investigation of the 3D-structure of the synthetic peptide will provide useful information for future vaccine and drug-design strategies.

HTLV-1 tropism and envelope receptor

“…A peptide corresponding to SU amino acid 197 to 216 (P197) was found to inhibit HTLV-1 Env-induced cell-cell fusion. This region lies in the PRR central domain (Figure 2), which is recognized by neutralizing antibodies (Ralston et al, 1989;Goetz et al, 1997), suggesting that this region is important for fusion to proceed. Based on these data, P197 was considered to mirror the HTLV Env receptor domain.…”