Impact of Side Chain Structure and Aglycon Carbonyl Group on the Immunostimulatory Activities of Semisynthetic Saponin Adjuvants

High Resolution Image Download MS PowerPoint Slide VSA-1 and VSA-2 are recently developed semisynthetic saponin immunostimulants derived from natural Momordica saponins (MS) I and II, respectively, through the incorporation of a linear dodecyl or benzyl undecanoate side chain. In this study, a series of novel MS derivatives with systematically varied side-chain lengths and steric bulk were synthesized. Immunological evaluation revealed that for MS I derivatives, adjuvant activity increased with side-chain elongation from C8 to C12 but declined upon further extension to C16. Enhancement of side-chain bulk, achieved by substituting the linear primary amide with a secondary amide, resulted in diminished adjuvant activity. In the case of MS II derivatives, either elongation or shortening of the side chain relative to –(CH 2 ) 10 COOBn led to loss of immunostimulatory function, as evidenced by reduced IgG1 and IgG2a production. Furthermore, for both VSA-1 and VSA-2, reduction of the C23 carbonyl group to a primary hydroxyl group completely abolished the adjuvant activity.