Characterization of peptide-pyrazole interactions in solution by low-temperature NMR studies.
Complexation of the amino- and carboxyl-protected tripeptide Piv-L-Val-L-Val-L-Val-tBu with 3-methylpyrazole and 3-amino-5-methylpyrazole was studied by low-temperature NMR experiments in a freonic solvent. The peptide forms an extended beta-type structure at all temperatures and associates through hydrogen bonding with the two pyrazole-based beta-sheet ligands. A detailed structural characterization of the formed complexes by one- and two-dimensional NMR experiments under slow exchange conditions was made possible by employing very low temperatures. The tripeptide associates to stable antiparallel dimers that are symmetrically capped on both sides by two pyrazole receptors to form 2:2 complexes. Amide groups of two neighboring residues in an extended conformation are involved in cyclic hydrogen bonds to the pyrazole. Based on amide chemical shift changes, the relative strength of intermolecular hydrogen bonds can be assessed and correlated with the electronic effects of the substituents on the pyrazole.
Wang
Wei
W
Freie Universität Berlin, Institut für Organische Chemie, Takustrasse 3, 14195 Berlin, Germany.
Weisz
Klaus
K
D001665:Binding Sites; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry; D013329:Structure-Activity Relationship; D013696:Temperature
D010455:Peptides; D011720:Pyrazoles; D012996:Solutions