Laboratorio de Biotransformaciones y Química de Ácidos Nucleicos, Universidad Nacional de Quilmes, Bernal 1876, Argentina.
Departamento de Química Bio-Orgánica, Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
Biomolecules. 2024 Jun 25;14(7):750. doi: 10.3390/biom14070750.
Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from , and fuculose-1-phosphate aldolase from , were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed.
二羟丙酮磷酸（DHAP）依赖性醛缩酶催化 DHAP 与各种醛的醛醇加成，生成具有两个手性中心的化合物。该反应可用于合成手性无环核苷，目前已广泛应用于抗病毒药物。在这些化合物中，模拟开环戊糖残基的脂肪链的手性对于活性至关重要。在本工作中，使用了三种 DHAP 依赖性醛缩酶：兔肌果糖-1,6-二磷酸醛缩酶、 Rhammulose-1-磷酸醛缩酶和 Fuculose-1-磷酸醛缩酶作为生物催化剂。胸腺嘧啶和胞嘧啶的醛衍生物被用作受体底物，生成转化率为 70%至 90%的新型无环核苷类似物，其中含有两个新的手性中心。此外，通过分子对接进行结构分析，深入了解观察到的非对映过量。
