Dalcetrapib and reduced glutathione effect on hemoglobin S polymerization studied by NMR

The effects of dalcetrapib (dal) and reduced glutathione (GSH) on a hemoglobin S (HbS) polymerization process are quantitatively evaluated using proton ( 1 H) magnetic relaxation. The HbS samples were obtained, using classical methods (centrifuging, decanting, and freezing–thawing cycles), starting from whole blood of voluntary patients suffering sickle cell disease (SCD). The transversal 1 H magnetic relaxation time ( T 2 ) was determined at 36 °C using the Carr-Purcell-Meiboom-Gill (CPMG) experiment (echo time: 1000 μs, 1000 echoes, 90° and 180° pulses of equal amplitude, and with 5 μs and 10 μs of width respectively), and its temporal behavior was used to obtain the initial ( T 2i ) and final ( T 2f ) values of T 2 as well as the delay time ( t d ) of the HbS polymerization process. Both compounds showed an effect on the HbS polymerization process with increments of t d in the 60% of the samples treated with GSH, as well as an increase of T 2i and T 2f in the 100% of the samples treated with dal. The changes in these parameters indicate, in both cases, an inhibition of the HbS polymerization processes.