Binding of Lanthanide Complexes to Histidine‐Containing Peptides Probed by Raman Optical Activity Spectroscopy

• Published in: Chemistry : a European journal 2018-06, Vol.24 (34), p.8664-8669
• Main Authors: Brichtová, Eva, Hudecová, Jana, Vršková, Nikola, Šebestík, Jaroslav, Bouř, Petr, Wu, Tao
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding; Binding Sites; biomolecular probe; Biomolecules; chemical imaging; Chemistry; circularly polarized luminescence; Coordination Complexes - chemistry; Histidine; Histidine - chemistry; Hydrogen-Ion Concentration; lanthanide-binding peptide; Lanthanoid Series Elements - chemistry; Luminescence; Molecular chains; Molecular dynamics; Molecular Dynamics Simulation; Optical activity; Peptides; Peptides - chemistry; Protein Binding; Protein Conformation; Proteins; Raman optical activity; rare earths; Spectroscopy; Thermodynamics
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201800840

Lanthanide complexes are used as convenient spectroscopic probes for many biomolecules. Their binding to proteins is believed to be enhanced by the presence of histidine, but the strength of the interaction significantly varies across different systems. To understand the role of peptide length and sequence, short histidine‐containing peptides have been synthesized (His‐Gly, His‐Gly‐Gly, His‐Gly‐Gly‐Gly, Gly‐His, Gly‐His‐Gly, His‐His, and Gly‐Gly‐His) and circularly polarized luminescence (CPL) induced at the [Eu(dpa)3]3− complex has been measured by means of a Raman optical activity (ROA) spectrometer. The obtained data indicate relatively weak binding of the histidine residue to the complex, with a strong participation of other parts of the peptide. Longer peptides, low pH, and a histidine residue close to the N‐peptide terminus favor the binding. The binding strengths are approximately proportional to the CPL intensity and roughly correlate with predictions based on molecular dynamics (MD) simulations. The specificity of lanthanide binding to the peptide structure and its intense luminescence and high optical activity make the ROA/CPL technique suitable for probing secondary and tertiary structures of peptides and proteins. Discerning Eu complex–peptide interactions: Circularly polarized luminescence of an achiral europium complex, as induced by seven model histidine‐containing peptides, has been detected by Raman optical activity spectrometry (see graphic) and rationalized by molecular dynamics simulations. The sensitivity and specificity of the signal for each peptide promises future usage in optical probes of peptide and protein structure in chemical imaging and medical diagnosis.