chemistry

Globo H

Globo H is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Globo H rather than just read about it. In short: Globo H (globohexaosylceramide) is a globo-series glycosphingolipid antigen that is present on the outer membrane of some cancer cells. Globo H is not expressed in normal tissue cells, but is expressed in a number of types of cancers, including cancers of the breast, prostate, and pancreas.

Key takeaways

Globo H belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Globo H to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Globo H from memory before moving on to harder problems.

Reference excerpt

Globo H (globohexaosylceramide) is a globo-series glycosphingolipid antigen that is present on the outer membrane of some cancer cells. Globo H is not expressed in normal tissue cells, but is expressed in a number of types of cancers, including cancers of the breast, prostate, and pancreas. Globo H's exclusivity for cancer cells makes it a target of interest for cancer therapies.

Structure

Defined by the monoclonal antibody MBr1, Globo H has been isolated from breast cancer cell line MCF-7, and its structure has been determined through several analyses, including NMR spectroscopy and methylation analysis. Globo H consists of a hexasaccharide of the structure Fucα(1-2)Galβ(1-3)GalNAcβ(1-3)Galα(1-4)Galβ(1-4)Glcβ(1) with a ceramide attached to its terminal glucose ring at the 1 position in a beta linkage.

Synthesis

Biosynthesis

Globo H's biosynthetic pathway is involved in the synthesis pathways of other globo-series glycosphingolipid antigens that are also specific to cancer cells, including stage-specific embryonic antigen-3 (SSEA3) and stage-specific embryonic antigen-4 (SSEA4). The biosynthetic pathway of these antigens includes the enzyme β 1,3-galactosyltransferase V (β3GalT5). β3GalT5 catalyzes the galactosylation of globoside-4 (Gb4) to SSEA3. SSEA3 can then be converted to SSEA4 by sialyltransferase adding a sialic acid group to its end, or it can be converted to Globo H by fucosyltransferase adding a fucose ring to its end. Playing a part in the formation of three different cancer-specific antigens, β3GalT5 is of particular interest in its relevance to cancer treatment, and it has been shown to be critical for cancer cell survival.

Chemical Synthesis In order to study its potential as a cancer therapy target, Globo H has been synthesized in the laboratory. One synthesis is achieved by first building two trisaccharides from their component sugars, and then linking them. The trisaccharides, with most of their functional groups protected to prevent side reactions, are linked by creating the GalNAcβ(1-3)Gal bond. A thioethyl group is added to the 1 position on one of the protected galactose rings, and in the presence of methyl triflate, this reacts with the hydroxyl group on the 3 position of the other galactose to link the trisaccharides and form the hexasaccharide. The ceramide is added to the 1 position of the terminal glucose ring after hexasaccharide formation.

Globo H as a Therapeutic Target As a Tumor Associated Carbohydrate Antigen (TACA), Globo-H is a promising clinical target for immunotherapy. While absent in normal tissues, the glycosphingolipid is overexpressed in a variety of epithelial cancer cell types including human pancreatic, gastric, lung, colorectal, esophageal, and breast tumors.

Globo H Anticancer Vaccines Globo-H's TACA character allows for its utilization as an anticancer vaccine, inducing antibody response against the epitope. The resulting humoral immunity could enable the selective eradication of Globo H-presenting tumors. The Taiwanese biopharma company OBI Pharma, Inc., was first to develop Adagloxad Simolenin (OBI-822), a Globo H hexasaccharide conjugated with the immunostimulatory carrier protein KLH. The Phase III GLORIA study is underway evaluating the carbohydrate-based immunogen's effects in high risk triple-negative breast cancer (TNBC) patients with an estimated completion date in 2027. Alternative vaccine conjugates have been developed which avoid issues associated with the protein carrier KLH by substituting it with a lipid or carbohydrate-based carrier. Examples include the use of lipid A derivatives or entirely carbohydrate vaccine conjugates such as Globo H-PS A1

Anti-Globo H Antibodies Globo H-targeting antibodies are another strategy currently being evaluated in the cancer therapeutic space. OBI Pharma's OBI-888 is a humanized IgG1 antibody that selectively binds to the Globo H antigen among other Globo series glycosphingolipids such as SSEA-3 and SSEA-4. Additionally, in vivo studies of OBI-888 in various Globo H-positive (GH+) xenografts models showed promising tumor growth inhibition results. OBI-888's human Phase I/II study for the treatment of metastatic and locally advanced solid tumors is estimated to finish in December 2022. Based on OBI-888, the first-in-class antibody-drug conjugate (ADC) 0BI-999 was additionally developed, linking OBI-888 to monomethyl auristatin E, a synthetic antineoplastic agent. The ADC is currently undergoing phase II trial in patients with advanced solid tumors, with an estimated completion date in Dec 2023. In Dec 2019 & Jan 2020, OBI-999 was granted two Orphan Drug Designations by the FDA for the treatment of pancreatic and gastric cancer.

References

Illustrations

Worked examples

Example 1 — a first encounter with Globo H

Start with the simplest possible case. Write down what Globo H claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Globo H before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Globo H ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Globo H

In research: Globo H appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Globo H in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Globo H is common in secondary-school and first-year university syllabi. It links to neighbouring topics Antigens, Biomolecules, Cancer immunotherapy, so understanding it makes those chapters shorter.
In everyday life: Look for Globo H outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Ask Teacher Smith questions about this articleOpens your AI tutor with a question about “Globo H” →

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Globo H in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Globo H means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Globo H out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Globo H in simple terms?

Why does Globo H matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Globo H?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Globo H.