Ambient addition of glucose reduces the O₂ transport capability of hemoglobin (Hb). Consequently, glycation is detrimental to human health and poses significant complications with diabetes, where poorly controlled blood sugar can result in twice normal addition levels. In spite of the importance of glycation, the mechanism by which it alters Hb function is unclear. We hypothesize interference with a functionally relevant motional dynamic in the protein. Recent NMR characterization of carbonmonoxy−Hb (HbCO) revealed a solution structure that is the average of the known solid−state structures, R and R₂ [Simplaceanu, et al. PNAS 2003]. The role of these conformations is uncertain. However, results suggested the existence of a functionally relevant R ↔ R₂ equilibrium. Through analysis of existing structures, we explored the relation of the primary sites of Hb glycation to those near the interface of sites involved in the purported R ↔ R₂ motion. This predicts steric interference of glycation with an R ↔ R₂ dynamic. We present initial progress towards dynamic NMR characterization of glycation−induced alteration of this equilibrium. This includes preparation of recombinant HbCO for NMR experiments on isotopically labeled samples, and a synthetic procedure for selective glycation of Hb at the N−terminus of the alpha chain. Ultimately, we will characterize differences between unmodified and selectively glycated HbCO using (1) ¹H−¹⁵N residual dipolar couplings for NMR structural characterization and (2) ¹⁵N spin relaxation to assess the rate and populations associated with R ↔ R₂.