Design, synthesis, and activity of 2,3-diphosphoglycerate analogs as allosteric modulators of hemoglobin O₂ affinity

Figures & data

Figure 1. Electrostatic interaction between the anionic charges of DPG and the cationic charges of amino acids present on the β subunits of Hb.

Scheme 1. Synthesis of diallyl phosphonate.

Scheme 2. Synthesis of alkyl phosphonates.

Scheme 3. Deprotection of the allyl group.

Table I. O₂ Binding properties of the Hb exposed to 2,3-DPG analogs.

Compound	P50 (mm Hg)	n
Control (cell-free Hb)	11.4	2.4
3	8.9	1.5
6	12.7	2.6
8	12.8	1.8
11	12.6	2.4

Conditions for P₅₀ and n determination: 30 μl of 400 mg/mL of Hb was added to 5 ml of Hemox solution (pH 7.4), 10 μl of anti-forming solution, 10 μl of additive B, 20 μl of BSA (TCS Scientific) with the 2,3-DPG analog at an analog:Hb molar ratio of 40:1 at 37°C for 45 min.

Figure 2. Oxygenation curve of Hb in the presence of 3, 6, 8, and 11.