title: The Biophysical Probes 2-fluorohistidine and 4-fluorohistidine: Spectroscopic Signatures and Molecular Properties.
abstract: Fluorinated amino acids serve as valuable biological probes, by reporting on local protein structure and dynamics through19F NMR chemical shifts. 2-fluorohistidine and 4-fluorohistidine, studied here with DFT methods, have even more capabilities for biophysical studies, as their altered pKavalues, relative to histidine, allow for studies of the role of proton transfer and tautomeric state in enzymatic mechanisms. Considering the two tautomeric forms of histidine, it was found that 2-fluorohistidine primarily forms the common (for histidine) τ-tautomer at neutral pH, while 4-fluorohistidine exclusively forms the less common π-tautomer. This suggests the two isomers of fluorohistidine can also serve as probes of tautomeric form within biomolecules, both by monitoring NMR chemical shifts and by potential perturbation of the tautomeric equilibrium within biomolecules. Fluorine also enables assignment of tautomeric states in crystal structures. The differences in experimental pKavalues between the isomers was found to arise from solvation effects, providing insight into the polarization and molecular properties of each isomer. Results also encompass13C and19F NMR chemical shifts, from both tautomers of 2-fluorohistidine and 4-fluorohistidine in a number of different environments. This work can serve as a guide for interpretation of spectroscopic results in biophysical studies employing 2-fluorohistidine and 4-fluorohistidine.
authors.affiliation: Department of Chemistry, Wichita State University, 1845 Fairmount Street, Wichita, KS 67260-0051, CV4 7AL, United States.
authors.forename: Chandana
authors.initials: C
authors.lastname: Kasireddy
authors.affiliation: Department of Chemistry, Wichita State University, 1845 Fairmount Street, Wichita, KS 67260-0051, CV4 7AL, United States.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Ellis
authors.affiliation: Department of Chemistry, Wichita State University, 1845 Fairmount Street, Wichita, KS 67260-0051, CV4 7AL, United States.
authors.forename: James G
authors.initials: JG
authors.lastname: Bann
authors.affiliation: Department of Chemistry, Wichita State University, 1845 Fairmount Street, Wichita, KS 67260-0051, CV4 7AL, United States.
authors.forename: Katie R
authors.initials: KR
authors.lastname: Mitchell-Koch
mesh_terms: D005456:Fluorescent Dyes / Q000737:chemistry*; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011522:Protons; D013057:Spectrum Analysis
chemical_list: C089806:4-fluorohistidine; D005456:Fluorescent Dyes; D011522:Protons; D006639:Histidine; C007749:2-fluorohistidine