4.8 Article

Synthesis as an Expanding Resource in Human Milk Science

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 143, Issue 30, Pages 11277-11290

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c05599

Keywords

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Funding

  1. National Science Foundation [1847804]
  2. National Institutes of Health [R35GM133602]
  3. American Chemical Society Petroleum Research Fund
  4. College of Arts & Science at Vanderbilt University
  5. Vanderbilt University
  6. Division Of Chemistry
  7. Direct For Mathematical & Physical Scien [1847804] Funding Source: National Science Foundation

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This article discusses methods for synthesizing and characterizing HMOs and mechanistic probes, emphasizing chemical, chemoenzymatic, and synthetic biology approaches. The paper concludes with a discussion of emergent challenges and opportunities for synthesis in human milk science, broadly defined.
Few classes of natural products rival the structural audacity of oligosaccharides. Their complexity, however, has stood as an immense roadblock to translational research, as access to homogeneous material from nature is challenging. Thus, while carbohydrates are critical to the myriad functional and structural aspects of the biological sciences, their behavior is largely descriptive. This challenge presents an attractive opportunity for synthetic chemistry, particularly in the area of human milk science. First, there is an inordinate need for synthesizing homogeneous human milk oligosaccharides (HMOs). Superimposed on this goal is the mission of conducting syntheses at scale to enable animal studies. Herein, we present a personalized rumination of our involvement, and that of our colleagues, which has led to the synthesis and characterization of HMOs and mechanistic probes. Along the way, we highlight chemical, chemoenzymatic, and synthetic biology based approaches. We close with a discussion on emergent challenges and opportunities for synthesis, broadly defined, in human milk science.

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