Human milk as a complex natural product.

Covering: up to the end of 2024Breastfeeding is one of the most effective ways to promote child health. However, characterizing the chemistry that fortifies the benefits of breastfeeding remains a grand challenge. Current efforts in the community are focused on characterizing the roles of the different carbohydrates, proteins, and fats in milk.

Evaluation of Kochetkov Hemiaminal hydrolysis under acidic, alkaline, and neutral conditions.

The most common precursors to synthetic glycoproteins are reducing end glycosyl amines. To afford these amines, a carbohydrate is reacted with an excess of an ammonia source to yield the β-anomer, exclusively, in a reaction known as the Kochetkov amination. Although this process is the state-of-the-art method to synthesize non-functionalized, β-amino (βA) glycans, misconceptions surrounding the stability of these amines has limited their use in subsequent reactions.

Synthesis of a Phosphoethanolamine Cellulose Mimetic and Evaluation of Its Unanticipated Biofilm Modulating Properties.

When coordinating and adhering to a surface, microorganisms produce a biofilm matrix consisting of extracellular DNA, lipids, proteins, and polysaccharides that are intrinsic to the survival of bacterial communities. Indeed, bacteria produce a variety of structurally diverse polysaccharides that play integral roles in the emergence and maintenance of biofilms by providing structural rigidity, adhesion, and protection from environmental stressors. While the roles that polysaccharides play in biofilm dynamics have been described for several bacterial species, the difficulty in isolating homogeneous material has resulted in few structures being elucidated.

A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism.

Observational evidence suggests that human milk oligosaccharides (HMOs) promote the growth of commensal bacteria in early life and adulthood. However, the mechanisms by which HMOs benefit health through modulation of gut microbial homeostasis remain largely unknown. 2'-fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and contributes to the essential health benefits associated with human milk consumption.

Total Synthesis of Ervaoffine J and K.

Herein, we describe the total synthesis of ervaoffine J & K from a central intermediate. Ervaoffine J was synthesized in eight steps in 14 % yield. Our strategy features an aerobic Winterfeldt oxidation to introduce the 4-quinolone moiety.

Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat.

Exposure to environmental toxicants (such as dioxins) has been epidemiologically linked to adverse reproductive health outcomes, including placental inflammation and preterm birth. However, the molecular underpinnings that govern these outcomes in gravid reproductive tissues remain largely unclear. Placental macrophages (also known as Hofbauer cells) are crucial innate immune cells that defend the gravid reproductive tract and help promote maternal-fetal tolerance.

The Utility of Human Milk Oligosaccharides against Group B Infections of Reproductive Tissues and Cognate Adverse Pregnancy Outcomes.

Preterm birth affects nearly 10% of all pregnancies in the United States, with 40% of those due, in part, to infections. (Group B , GBS) is one of the most common perinatal pathogens responsible for these infections. Current therapeutic techniques aimed to ameliorate invasive GBS infections are less than desirable and can result in complications in both the neonate and the mother.

A Hitchhiker's Guide to Problem Selection in Carbohydrate Synthesis.

Oligosaccharides are ubiquitous in molecular biology and are used for functions ranging from governing protein folding to intercellular communication. Perhaps paradoxically, the exact role of the glycan in most of these settings is not well understood. One reason for this contradiction concerns the fact that carbohydrates often appear in heterogeneous form in nature.

Gram-Scale Total Synthesis of (±)-Ibogamine.

We describe the gram-scale total synthesis of (±)-ibogamine in nine steps and 24% overall yield. The approach features a Mitsunobu fragment coupling and macrocyclic Friedel-Crafts alkylation to establish the nitrogen-containing core of ibogamine. A regio- and diastereoselective hydroboration allows for simultaneous formation of the tetrahydroazepine and isoquinuclidine ring systems via sulfonamide deprotection and concomitant intramolecular cyclization.

Juneteenth in STEMM and the barriers to equitable science.

We are 52 Black scientists. Here, we establish the context of Juneteenth in STEMM and discuss the barriers Black scientists face, the struggles they endure, and the lack of recognition they receive. We review racism's history in science and provide institutional-level solutions to reduce the burdens on Black scientists.

Anti-biofilm Activity of Human Milk Oligosaccharides in Clinical Strains of Streptococcus agalactiae with Diverse Capsular and Sequence Types.

Group B Streptococcus (GBS) is an encapsulated Gram-positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short-chain sugars that have recently been shown to possess antimicrobial and anti-biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS.

Streptococcus agalactiae Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy.

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a Gram-positive encapsulated bacterium that colonizes the gastrointestinal tract of 30 to 50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues.

Ameliorating adverse perinatal outcomes with Lactoferrin: An intriguing chemotherapeutic intervention.

Adverse pregnancy outcomes affect 54 million people globally per year, with at least 50% of these attributed to infection during gestation. These include inflammation of the membranes surrounding the growing fetus (chorioamnionitis), preterm prelabor rupture of membranes (PPROM), preterm birth (PTB), early-onset disease (EOD) and late-onset disease (LOD), neonatal and maternal sepsis, and maternal or fetal demise. Although universal screening and implementation of intrapartum antibiotic prophylaxis (IAP) has improved EOD outcomes, these interventions have not reduced the incidences of LOD or complications occurring early on during pregnancy such as PPROM and PTB.

Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy.

Perinatal infection with Streptococcus agalactiae, or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant, cadD.

Recent advances on human milk oligosaccharide antimicrobial activity.

Over the past century, human health has been enhanced by antimicrobial development. Following the deployment of the first antibiotics in the 1940s, bacterial resistance evolved and has increasingly outmaneuvered even the most promising antimicrobial agents. Accordingly, increased interest has been placed on alternative methods to circumvent antimicrobial resistance evolution.

Synthesis of the Aeromonas veronii strain Bs8 disaccharide repeating unit.

Presented herein is the synthesis of the Aeromonas veronii disaccharide repeating unit which has been achieved in 11 steps starting from d-fucose and d-galactosamine.

Antibiofilm Activity of Human Milk Oligosaccharides against Multidrug Resistant and Susceptible Isolates of .

is a serious threat to human health, per the Centers for Disease Control and Prevention's latest threat assessment. is a Gram-negative opportunistic bacterial pathogen that causes severe community and nosocomial infections in immunocompromised patients. Treatment of these infections is confounded by the emergence of multi- and pan-drug resistant strains of .

Galacto-Oligosaccharide Supplementation Modulates Pathogen-Commensal Competition between Streptococcus agalactiae and Streptococcus salivarius.

The members of the infant microbiome are governed by feeding method (breastmilk vs. formula). Regardless of the source of nutrition, a competitive growth advantage can be provided to commensals through prebiotics - either human milk oligosaccharides (HMOs) or plant oligosaccharides that are supplemented into formula.

Analysis of Susceptibility to the Antimicrobial and Anti-Biofilm Activity of Human Milk Lactoferrin in Clinical Strains of With Diverse Capsular and Sequence Types.

Group B (GBS) is one of the leading infection-related causes of adverse maternal and neonatal outcomes. This includes chorioamnionitis, which leads to preterm ruptures of membranes and can ultimately result in preterm or stillbirth. Infection can also lead to maternal and neonatal sepsis that may contribute to mortality.

2'-Fucosyllactose Ameliorates Chemotherapy-Induced Intestinal Mucositis by Protecting Intestinal Epithelial Cells Against Apoptosis.

Background & Aims: Intestinal mucositis, a severe complication of antineoplastic therapeutics, is characterized by mucosal injury and inflammation in the small intestine. Therapies for the prevention and treatment of this disease are needed. We investigated whether 2'-fucosyllactose (2'-FL), an abundant oligosaccharide in human milk, protects intestinal integrity and ameliorates intestinal mucositis.

The Diverse Antimicrobial Activities of Human Milk Oligosaccharides against Group B Streptococcus.

Streptococcus agalactiae or Group B Streptococcus (GBS) is a Gram-positive bacterial pathobiont that is the etiological cause of severe perinatal infections. GBS can colonize the vagina of pregnant patients and invade tissues causing ascending infections of the gravid reproductive tract that lead to adverse outcomes including preterm birth, neonatal sepsis, and maternal or fetal demise. Additionally, transmission of GBS during labor or breastfeeding can also cause invasive infections of neonates and infants.

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids.

The arimetamycin A glycan governs the compound's cytotoxicity (IC). To study this branched, deoxy-amino disaccharide, we designed and synthesized a modified acyl donor that underwent glycosylation with three anthracycline aglycones: steffimycinone, daunorubicinone, and doxorubicinone. The result of the approach was a synthesis of arimetamycin A and two novel hybrid anthracyclines.

Total Synthesis of the ssp. 3240 Zwitterionic Trisaccharide Repeating Unit.

Zwitterionic carbohydrate modifications, such as phosphoethanolamine (PEtN), govern host-pathogen interactions. Whereas it is recognized that these modifications stimulate the host immune system, the purpose of PEtN modification remains largely descriptive. As an enabling step toward studying this carbohydrate modification, we report a synthesis of the zwitterionic trisaccharide repeating unit.