The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development

Biochem Biophys Res Commun. 2017 Mar 11;484(3):501-507. doi: 10.1016/j.bbrc.2017.01.077. Epub 2017 Jan 19.

Abstract

Analysis of our Plasmodium falciparum malaria parasite peptides' 1H-NMR database in the search for H-bonds and π-interactions led us to correlate their presence or absence with a peptide's particular immunological behavior. It was concluded that a 26.5 ± 1.5 Å between positions 1 to 9 of the HLA-DRβ1* interacting region was necessary for proper docking of 20mer-long peptides and these MHC Class II molecules for full-protective immunity. Presence of intramolecular H-bonds or π-interactions leading to righ-handed α-helix or β-turn conformation in this peptide's region induces different immune responses or none. PPIIL conformation and the absence of any intramolecular interaction thus became the first feature characterising our immune protection-inducing structures as malaria vaccine candidates.

Keywords: Hydrogen bond; Malaria; TCR-peptide-MHC complex; X—H-π interaction.

MeSH terms

  • Binding Sites
  • Drug Design*
  • HLA-DRB1 Chains / chemistry
  • HLA-DRB1 Chains / ultrastructure
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / ultrastructure*
  • Hydrogen Bonding
  • Malaria Vaccines / chemistry*
  • Peptides / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping / methods*
  • Sequence Analysis, Protein
  • Structure-Activity Relationship
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / ultrastructure

Substances

  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II
  • Malaria Vaccines
  • Peptides
  • Vaccines, Synthetic