Open AccessVaccine Adjuvants Derivatized from Momordica Saponins I and II
Author(s) -
Pengfei Wang,
Xiong Ding,
Hyun-Jung Kim,
Đani Škalamera,
Suzanne M. Michalek,
Ping Zhang
Publication year - 2019
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.9b01511
Subject(s) - chemistry , saponin , adjuvant , immunostimulant , toxicity , natural product , immune system , immunoadjuvant , pharmacology , biochemistry , stereochemistry , organic chemistry , immunology , biology , medicine , alternative medicine , pathology
We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 ( 5 ), the derivative of MS I, potentiates a significantly higher IgG2a responose than the corresponding natural product. Its IgG1 and IgG2a production is similar to that of GPI-0100, indicating a potential mixed and antigen-specific Th1/Th2 immune response, which is different from the Th2 immunity induced by the natural saponin MS I. In addition, toxicity evaluations show that adjuvant VSA-1 ( 5 ) is much less toxic than the widely used natural saponin mixture Quil A. These results prove that derivatizing Momordica saponins can be a viable way for easy access to structurally defined saponin immunostimulants with favorable adjvuant activity and low toxicity.