Q7. The notion of treating sickle cell disease (SCD) by stabilizing the R (oxy) conformation was

introduced by Beutler. He proposed that converting a fraction of sickle hemoglobin (HbS) to the

oxidized form or to the carbon monoxide complex of HbS would reduce sickling by maintaining a

fraction of HbS molecules in the nonpolymerizing R conformation of oxyhemoglobin, while

understanding that such a treatment would compromise oxygen delivery to the tissues.

Solution

000

↑↓

от

R

Polymer/nA. How will you measure the kinetics of this reaction? Below are only one of the two options available

to you (3+3 = 6 points total).

i. Oxygen tank and the dark (non fluorescent) dye shown below

ii. Ultracentrifuge and uv-vis absorbance

Juge

R

Fluorescent

Dark/nCompound 9;

compound 23;

Len 2

Val 73

Ser 131

Ser 131

Arg 141

The 134

Au 78

Ser 131

al

Asp 75

Val 1

al

Met 76

Val 73

B. Based on the PDB structures, which compound will have higher affinity for Hb? Explain your

answer based on molecular interactions between the compound and the structure of Hb (you may

need to look at the relevant paper from hints)