title: The effect of relaxation on the epitope mapping by saturation transfer difference NMR.
abstract: The effect of longitudinal relaxation of ligand protons on saturation transfer difference (STD) was investigated by using a known binding system, dihydrofolate reductase and trimethoprim. The results indicate that T1 relaxation of ligand protons has a severe interference on the epitope map derived from a STD measurement. When the T1s of individual ligand protons are distinctly different, STD experiments may not give an accurate epitope map for the ligand-target interactions. Measuring the relaxation times prior to mapping is strongly advised. A saturation time shorter than T1s is suggested for improving the potential epitope map. Reduction in temperature was seen to enhance the saturation efficiency in small to medium size targets.
authors.affiliation: Discovery Chemistry Research and Technologies, Lilly Research Labs, Lilly Corporate Center, Eli Lilly & Co, Indianapolis, IN 46285, USA.
authors.forename: Jiangli
authors.initials: J
authors.lastname: Yan
authors.forename: Allen D
authors.initials: AD
authors.lastname: Kline
authors.forename: Huaping
authors.initials: H
authors.lastname: Mo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shapiro
authors.forename: Edward R
authors.initials: ER
authors.lastname: Zartler
mesh_terms: D000818:Animals; D002417:Cattle; D018604:Epitope Mapping / Q000379:methods*; D008099:Liver / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011485:Protein Binding; D011522:Protons; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*; D014295:Trimethoprim / Q000737:chemistry*
chemical_list: D011522:Protons; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase