Ulijn Rein V, De Martin Luigi, Gardossi Lucia, Janssen Anja E M, Moore Barry D, Halling Peter J
Department of Pure and Applied Chemistry, Strathclyde University, Glasgow G1 1XW.
Biotechnol Bioeng. 2002 Dec 5;80(5):509-15. doi: 10.1002/bit.10396.
Thermolysin catalyzed solid-to-solid synthesis of the model peptide Z-L-Phe-L-Leu-NH(2) is practically feasible in water and a range of organic solvents with different physicochemical properties. Excellent overall conversions were obtained in acetonitrile, ethyl acetate, n-hexane, methanol, 2-propanol, tert-amyl alcohol, tetrahydrofuran, toluene and water, while no product precipitation was observed in dichloromethane resulting in a much lower yield. In precipitation driven synthesis the product accumulates both in solution and in the solid phase. It was shown that the highest overall yields (yield in the liquid plus yield in the solid) can be expected in solvents where the substrate solubilities are minimized. The best yields of solid product can be expected in solvents where both product and substrate solubilities are lowest. This was in agreement with experimental observations and should be generally valid.
嗜热菌蛋白酶催化的模型肽Z-L-苯丙氨酸-L-亮氨酸-NH₂的固-固合成在水和一系列具有不同物理化学性质的有机溶剂中实际上是可行的。在乙腈、乙酸乙酯、正己烷、甲醇、2-丙醇、叔戊醇、四氢呋喃、甲苯和水中获得了优异的总转化率，而在二氯甲烷中未观察到产物沉淀，导致产率低得多。在沉淀驱动的合成中，产物在溶液和固相中都会积累。结果表明，在底物溶解度最小的溶剂中可预期获得最高的总产率（液相产率加固相产率）。在产物和底物溶解度都最低的溶剂中可预期获得最高的固体产物产率。这与实验观察结果一致，并且应该普遍适用。
