Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemical Synthesis of Human Milk Oligosaccharides: para-Lacto-N-hexaose and para-Lacto-N-neohexaose.

ABSTRACT: Human milk oligosaccharides (HMO) have emerged as a very active area of research in glycoscience and nutrition. HMO are involved in the early development of infants and may help to prevent certain diseases. The development of chemical methods for obtaining individual HMO aids the global effort dedicated to understanding the roles of these biomolecules. Reported herein is the chemical synthesis of two common core hexasaccharides found in human milk, i. e. para-lacto-N-hexaose (pLNH) and para-lacto-N-neohexaose (pLNnH). After screening multiple leaving groups and temporary protecting group combinations, a 3+3 convergent coupling strategy was found to work best for obtaining these linear glycans.

SUBMITTER: Singh Y

PROVIDER: S-EPMC11370726 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Chemical Synthesis of Human Milk Oligosaccharides: para-Lacto-N-hexaose and para-Lacto-N-neohexaose.

Singh Yashapal Y Escopy Samira S Shadrick Melanie M Bandara Mithila D MD Stine Keith J KJ Demchenko Alexei V AV

Chemistry (Weinheim an der Bergstrasse, Germany) 20231006 64

Human milk oligosaccharides (HMO) have emerged as a very active area of research in glycoscience and nutrition. HMO are involved in the early development of infants and may help to prevent certain diseases. The development of chemical methods for obtaining individual HMO aids the global effort dedicated to understanding the roles of these biomolecules. Reported herein is the chemical synthesis of two common core hexasaccharides found in human milk, i. e. para-lacto-N-hexaose (pLNH) and para-lact ...[more]

PMID: 37639512

Similar Datasets

The chemical synthesis of human milk oligosaccharides: Lacto-N-tetraose (Galβ1→3GlcNAcβ1→3Galβ1→4Glc).

Project description:The total chemical synthesis of lacto-N-tetraose (LNT) has been completed using both convergent and linear strategies. Similarly to that of our previous HMO syntheses, the donor-acceptor protecting-leaving group combinations were found to be of paramount significance to achieving successful glycosylations and minimizing side reactions.

| S-EPMC6897367 | biostudies-literature

The chemical synthesis of human milk oligosaccharides: Lacto-N-neotetraose (Galβ1→4GlcNAcβ1→3Galβ1→4Glc).

Project description:The discovery of innovative methods that offer new capabilities for obtaining individual oligosaccharides from human milk will help to improve understanding their roles and boost practical applications. The total chemical synthesis of lacto-N-neotetraose (LNnT) has been completed using both linear and convergent strategies. The donor and acceptor protecting and leaving group combinations were found to be of paramount significance to successful couplings.

| S-EPMC6717531 | biostudies-literature

Chemical synthesis of human milk oligosaccharides: lacto-N-neohexaose (Galβ1 → 4GlcNAcβ1→)<sub>2</sub> 3,6Galβ1 → 4Glc.

Project description:The first chemical synthesis of lacto-N-neohexaose (LNnH) has been completed using a convergent synthetic strategy. The reaction conditions and donor-acceptor combinations have been carefully refined to minimize side reactions and achieve high yields in all glycosylation steps. Lacto-N-neotetraose, another common human milk oligosaccharide, was also synthesized en route to the target LNnH.

| S-EPMC7658587 | biostudies-literature

Chemical Synthesis of Human Milk Oligosaccharides: Lacto-<i>N</i>-hexaose Galβ1→3GlcNAcβ1→3 [Galβ1→4GlcNAcβ1→6] Galβ1→4Glc.

Project description:The first synthesis of lacto-N-hexaose (LNH) has been completed using a convergent strategy. The donor-acceptor protecting-leaving group combinations were found to be of paramount significance for achieving successful glycosylations and minimizing side reactions. Lacto-N-tetraose, another common human milk oligosaccharide, was also obtained en route to the target LNH.

| S-EPMC8114087 | biostudies-literature

Inefficient Metabolism of the Human Milk Oligosaccharides Lacto-N-tetraose and Lacto-N-neotetraose Shifts Bifidobacterium longum subsp. infantis Physiology.

Project description:Human milk contains a high concentration of indigestible oligosaccharides, which likely mediated the coevolution of the nursing infant with its gut microbiome. Specifically, Bifidobacterium longum subsp. infantis (B. infantis) often colonizes the infant gut and utilizes these human milk oligosaccharides (HMOs) to enrich their abundance. In this study, the physiology and mechanisms underlying B. infantis utilization of two HMO isomers lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) was investigated in addition to their carbohydrate constituents. Both LNT and LNnT utilization induced a significant shift in the ratio of secreted acetate to lactate (1.7-2.0) in contrast to the catabolism of their component carbohydrates (~1.5). Inefficient metabolism of LNnT prompts B. infantis to shunt carbon toward formic acid and ethanol secretion. The global transcriptome presents genomic features differentially expressed to catabolize these two HMO species that vary by a single glycosidic linkage. Furthermore, a measure of strain-level variation exists between B. infantis isolates. Regardless of strain, inefficient HMO metabolism induces the metabolic shift toward formic acid and ethanol production. Furthermore, bifidobacterial metabolites reduced LPS-induced inflammation in a cell culture model. Thus, differential metabolism of milk glycans potentially drives the emergent physiology of host-microbial interactions to impact infant health.

| S-EPMC5989456 | biostudies-literature

Bifidobacterium breve UCC2003 metabolises the human milk oligosaccharides lacto-N-tetraose and lacto-N-neo-tetraose through overlapping, yet distinct pathways.

Project description:In this study, we demonstrate that the prototype B. breve strain UCC2003 possesses specific metabolic pathways for the utilisation of lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), which represent the central moieties of Type I and Type II human milk oligosaccharides (HMOs), respectively. Using a combination of experimental approaches, the enzymatic machinery involved in the metabolism of LNT and LNnT was identified and characterised. Homologs of the key genetic loci involved in the utilisation of these HMO substrates were identified in B. breve, B. bifidum, B. longum subsp. infantis and B. longum subsp. longum using bioinformatic analyses, and were shown to be variably present among other members of the Bifidobacterium genus, with a distinct pattern of conservation among human-associated bifidobacterial species.

| S-EPMC5144078 | biostudies-literature

Synthesis of asymmetrical multiantennary human milk oligosaccharides.

Project description:Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability.

| S-EPMC5502611 | biostudies-literature

Infant-gut associated Bifidobacterium dentium strains utilize the galactose moiety and release lacto-N-triose from the human milk oligosaccharides lacto-N-tetraose and lacto-N-neotetraose.

Project description:Much evidence suggests a role for human milk oligosaccharides (HMOs) in establishing the infant microbiota in the large intestine, but the response of particular bacteria to individual HMOs is not well known. Here twelve bacterial strains belonging to the genera Bifidobacterium, Enterococcus, Limosilactobacillus, Lactobacillus, Lacticaseibacillus, Staphylococcus and Streptococcus were isolated from infant faeces and their growth was analyzed in the presence of the major HMOs, 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), 2',3-difucosyllactose (DFL), lacto-N-tetraose (LNT) and lacto-N-neo-tetraose (LNnT), present in human milk. Only the isolated Bifidobacterium strains demonstrated the capability to utilize these HMOs as carbon sources. Bifidobacterium infantis Y538 efficiently consumed all tested HMOs. Contrarily, Bifidobacterium dentium strains Y510 and Y521 just metabolized LNT and LNnT. Both tetra-saccharides are hydrolyzed into galactose and lacto-N-triose (LNTII) by B. dentium. Interestingly, this species consumed only the galactose moiety during growth on LNT or LNnT, and excreted the LNTII moiety. Two β-galactosidases were characterized from B. dentium Y510, Bdg42A showed the highest activity towards LNT, hydrolyzing it into galactose and LNTII, and Bdg2A towards lactose, degrading efficiently also 6'-galactopyranosyl-N-acetylglucosamine, N-acetyl-lactosamine and LNnT. The work presented here supports the hypothesis that HMOs are mainly metabolized by Bifidobacterium species in the infant gut.

| S-EPMC8639736 | biostudies-literature

Chemoenzymatic Synthesis of a Library of Human Milk Oligosaccharides.

Project description:Human milk oligosaccharides (HMOs) are a family of diverse unconjugated glycans that exist in human milk as one of the major components. Characterization, quantification, and biofunctional studies of HMOs remain a great challenge due to their diversity and complexity. The accessibility of a homogeneous HMO library is essential to solve these issues which have beset academia for several decades. In this study, an efficient chemoenzymatic strategy, namely core synthesis/enzymatic extension (CSEE), for rapid production of diverse HMOs was reported. On the basis of 3 versatile building blocks, 3 core structures were chemically synthesized via consistent use of oligosaccharyl thioether and oligosaccharyl bromide as glycosylation donors in a convergent fragment coupling strategy. Each of these core structures was then extended to up to 11 HMOs by 4 robust glycosyltransferases. A library of 31 HMOs were chemoenzymatically synthesized and characterized by MS and NMR. CSEE indeed provides a practical approach to harvest structurally defined HMOs for various applications.

| S-EPMC5953189 | biostudies-literature

Controllable Enzymatic Synthesis of Natural Asymmetric Human Milk Oligosaccharides.

Project description:Among human milk oligosaccharides (HMOs), linear HMOs are synthesized through mature but varied routes. Although branched HMOs can be synthesized by chemical, enzymatic, or chemoenzymatic methods, these methods cannot be easily applied to the synthesis of asymmetric multiantennary oligosaccharides. Herein, we developed a controllable method to synthesize asymmetric biantennary HMOs. In our synthetic route, GlcNAcβ1,3(GlcN3β1,6)Glaβ1,4Glc was first chemically synthesized as the core tetrasaccharide, which contains β1,6GlcN3 as the "stop" sugar in transferase-catalyzed glycosylation. The desired sugars at the GlcNAcβ1-3Gal arm can be assembled using galactosyltransferase, N-acetylglucosaminyltransferase, and fucosyltransferase. Then, the Staudinger reduction and acetylation were used to transform GlcN3 to GlcNAc and assemble sugars by initiating the "go" process. By manipulating transferase-catalyzed glycosylations, 22 natural asymmetric biantennary oligosaccharides were synthesized.

| S-EPMC11600167 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data