Designer phospholipids – structural retrieval, chemo-/bio- synthesis and isotopic labeling

Phospholipase D-Catalyzed Transphosphatidylation for the Synthesis of Rare Complex Phospholipid Species─Hemi-bis(monoacylglycero)phosphate and Bis(diacylglycero)phosphate

“…Apart from the reaction conditions discussed above, the character of the fatty acid residues is incorporated into the glycerol backbones of the MAGs/DAGs, directly defining the affinity and efficiency of the transphosphatidylation. The structural variations of the attached fatty acid residues, carbon chain length, unsaturation level, and unsaturation position not only affect the affinity toward the active site of PLD but also influence the overall physicochemical properties of the molecules . Small variations in the structures of the fatty acid residues can have a large impact on the optimal selection of reaction conditions, as observed for the hydrophobic DAGs/MAGs containing longer saturated fatty acids (stearic acid and docosanoic acid), which are significantly harder to dissolve in the designed biphasic reaction system.…”

“…The structural variations of the attached fatty acid residues, carbon chain length, unsaturation level, and unsaturation position not only affect the affinity toward the active site of PLD but also influence the overall physicochemical properties of the molecules. 16 Small variations in the structures of the fatty acid residues can have a large impact on the optimal selection of reaction conditions, as observed for the hydrophobic DAGs/MAGs containing longer saturated fatty acids (stearic acid and docosanoic acid), which are significantly harder to dissolve in the designed biphasic reaction system. All reactions with DAGs create cloudy heterogeneous systems, which already suggests that these transphosphatidylation reactions might be more efficient in other solvent systems.…”

“…10 The synthesis of structurally defined phospholipids can today be carried out through a range of different routes, complete de novo synthesis, biosynthetic systems, or chemical/ enzymatic modifications. 16 The most common approach involves enzyme or chemical-catalyzed modifications of more available and easily accessible naturally occurring phospholipid species, such as PC. 17 Enzymes provide a green alternative to the often harsh chemical catalysts used and provide the opportunity for regio-, stereo-, and chemoselective reactions, which, for example, allows for the substitutions of fatty acids at specific (sn-1/sn-2) positions of the glycerol backbone.…”

“…The synthesis of structurally defined phospholipids can today be carried out through a range of different routes, complete de novo synthesis, biosynthetic systems, or chemical/enzymatic modifications . The most common approach involves enzyme or chemical-catalyzed modifications of more available and easily accessible naturally occurring phospholipid species, such as PC .…”

A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs

“…The use of carbodiimide-based chemical coupling catalysts, in EDC and DMAP instead, has long been utilized efficiently for Steglich esterification reactions. However, the combination with GPC is far less frequently utilized and commonly accompanied by functionalized alcohol donors (e.g., chlorinated fatty acids) or lyso-PC . GPC has a strong hydrophilic character and is poorly soluble in many of the commonly used organic solvents (dichloromethane, pyridine, and tetrahydrofuran), which leads to challenging and less efficient assays.…”