Determining the Binding Affinity Between Calcium and the Phospholipid Analog, Cyclohexyl Phospho‐L‐Serine

Abstract

During apoptosis a ternary complex is formed between the phospholipid membrane surface of a cell, calcium metal ions, and a repair protein. The binding affinity and structural arrangement of this complex is not well characterized. Small molecule analogs of the phospholipid, phosphatidylserine (PS), are proposed to investigate the binding in the ternary complex. A phospolipid analog (PLA) of PS, cyclohexyl phospho‐L‐serine (cycPS), was previously synthesized. Isothermal titration calorimetry (ITC) was used to determine how the anionic phospho‐L‐serine head group of the proposed analog compares to PS in affinity to and selectivity for Ca2+ over Mg2+. The ITC method was first developed to measure Ca2+ binding by a similar commercially available compound, O‐phospho‐L‐serine, and then applied to the proposed analog, cycPS. Comparable Ca2+ binding affinity of cycPS relative to PS allows for further experiments with Mg2+ to evaluate if cycPS is a sufficient structural and biological model of PS. This research was made possible through funding from The College of Wooster.