Reversible inhibition of sheep liver sorbitol dehydrogenase by the antidiabetogenic drug 2‐hydroxymethyl‐4‐(4‐N,N‐dimethylaminosulfonyl‐1‐piperazino) pyrimidine

Substrate specificity of sheep liver sorbitol dehydrogenase

“…Due to the involvement of SDH in the etiology of diabetic complications, the enzyme has recently become a target for drug design (see [10,14] and references cited therein). The substrate specificity of SDH is a premise for prospective rational design of potent and specific enzyme inhibitors.…”

“…Recently, the potent SDH inhibitor 2-hydroxymethyl-4-(4-N,N-dimethylaminosulphonyl-1-piperazino)pyrimidine (SDI 158) was shown to have clinically beneficial effects in diabetic rat tissues [10,14]. At present, many investigators are attempting the synthesis of potent and specific SDH inhibitors for prospective clinical trials.…”

“…The substrate specificity of this enzyme is a premise for rational drug design, because substrate analogues can be expected to be optimally potent and specific inhibitors. It has been suggested that SDI 158 binds in the enzyme active site as a substrate analogue [10]. Derivatives of substrates, including polyols, deoxy polyols and aromatic alcohols, with an inhibitory group such as thiolate [14] in the reactive 2-position (e.g.…”

“…pathway in hyperglycaemia has been implicated in disease mechanisms [8][9][10]. Apart from its involvement in the production of fructose in seminal plasma and a possible function in coenzyme regulation [7], the physiological role of the polyol pathway in nondiabetics remains unclear.…”

Selective disruption of protein aggregation by cyclodextrin dimers

“…To examine this possibility, we have studied a group of enzymes, which are listed in Table 1 (12), and sorbitol dehydrogenase (13)], and adenosine deaminase is a monomeric enzyme (14). Our preliminary screen simply looked at whether CD dimers inhibited the enzyme's activity.…”