Cyclic analogue of human heat shock protein 70(29-42) fragment. Synthesis,conformational studies and evaluation of its immunogenicity

The cyclic hexadecapeptide containing human heat shock protein 70(29-42) fr agment cyclized by the disulfide bridge between two L-cysteine residues int roduced at the N- and C-termini was synthesized by the solid phase method. It was established that the cyclic analogue, contrary to its linear counter part, had much lower ability to generate immune response in rabbits. Confor mational studies of cyclic peptide performed using ID and 2D H-1-NMR spectr oscopy in conjunction with theoretical conformational analysis revealed tha t the cyclization constrained the 3D structure of this peptide, reflected b y the observed rate of cis/trans isomerization of Arg9-Thr10 peptide bond a nd the presence of Gly7-Asn8 peptide bond in cis geometry. We, therefore, p ostulate that the conformational flexibility in the case of Human Heat Shoc k Protein fragments is a key element for their immunogenicity.