201401 Isolation, Purification, and Synthesis of Human Milk Oligosaccharides with Antimicrobial Activity

A request for applications (RFA) with set aside is proposed, entitled “Isolation, Purification, and Synthesis of Human Milk Oligosaccharides with Antimicrobial Activity” using the R43 Small Business Innovation Research (SBIR) Grant - Phase I only and the R41 Small Business Technology Transfer (STTR) Grant - Phase I only grant mechanisms.


NICHD-supported investigators have discovered that some oligosaccharides in human milk have antimicrobial activity against enteric bacteria and viruses, including Campylobacter, E. coli, and noroviruses. The purpose of this RFA is to stimulate the small business community to develop innovative methods to: (1) identify human milk oligosaccharides (HMO) that have antimicrobial activity; (2) isolate and purify promising HMOs; (3) characterize the structure of these HMOs in order to develop a library of bioactive HMOs to serve as templates for chemical or biological synthesis of promising HMOs; (4) ramp up synthetic procedures using GMP to produce batches of HMOs in kilogram quantities for preclinical testing.


The scope of the RFA includes the isolation, purification, structural characterization, and synthesis of bioactive HMOs in kilogram quantities. The scope also includes developing new methods for assessing bioactivity of HMOs and for initiating novel structure-function studies to ascertain what HMO structures are most likely to bind to enteric microbes to prevent entry into enterocytes. Also within the scope of the RFA would be studies designed to ascertain the spectrum of microbes that particular HMOs can neutralize. Because HMOs do not interfere with the synthetic machinery of the microbes, it is unlikely that bacterial or viral resistance would develop against this class of antimicrobial agents. An important research thrust of the RFA will also be to build on knowledge generated by structure-function studies of oligosaccharides found in human milk by developing novel oligosaccharides not found in nature that may have greater antimicrobial bioactivity and/or that may have a wider spectrum of antimicrobial activity than HMOs found in nature.


The central objective of this initiative is to develop new GMP methods to generate quantities of purified HMOs with known antimicrobial activity in large enough quantities to begin preclinical testing. The ultimate objective of this initiative is to develop a new class of antimicrobial agents that are active against enteric organisms for use in clinical care as preventive agents or for treatment of enteric disease.

Program Contact

Gilman Grave, MD
Pediatric Growth and Nutruition Branch


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