with Hb amino groups, particularly the terminal α1val, and thereby increase O2 affinity. Amongst the most potent of the aromatic aldehydes tested was o-vanillin [9,30]. Its isomer p-vanillin (vanillin) is also thought to reactwith αHis103 to promote the oxy conformation, with possible other interactions at key sites of polymer contact (βHis116 and βHis117). In vivo, although vanillin itself is poorly absorbed, a pro-drugMX-1520 was shown to protect sickle rats against hypoxia