FAQ

 

1. Biological Background

    1.1 What are haptens?

    1.2 What is a carrier?

    1.3 How do haptens induce an immune response?

    1.4 What kinds of haptens are known?

    1.5 What are antibodies?

2. Contents of SuperHapten

    2.1 What data was compiled?

    2.2 Where do the structures originate?

    2.3 How were the haptens classified?

    2.4 What are 'putative' and 'confirmed' haptens?

    2.5 What are 'purchasable' and 'not available' haptens?

3. Using SuperHapten

    3.1 What is the "Search via Known Compounds"?

    3.2 What is the "Search via your own Structure"?

    3.3 What is the "Search for Similar Haptens"?

    3.4 How can I perfom a 2D Similarity Search against the database?

    3.5 What are the System Requirements for MDLŽ Chime for MDLŽ Chime?

4. Database Schema

 


What are haptens?

Haptens are small molecules, that can induce a response by the immune system. In contrast to antigens, haptens need to be bound to a larger molecule (the carrier) before they are recognized by the immune system.

 

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What is a carrier?

Carriers are macromolecules that bind haptens and enable them to induce an immune response. Most carriers are secretory proteins or proteins on the cell surface, where cells of the immune system can reach them. Additionally, some polymers are known to act as carriers. Depending on the type of carrier and hapten molecules, they bind each other by covalent bonding or non-covalent interactions that are sometimes mediated by additional molecules.

 

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How do haptens induce an immune response?

First, a hapten is bound to its carrier. The carrier, normally ignored by the immune system now has a different surface structure that can act as an antigen (the hapten on its own is too small). Depending on the type of immune cell that recognizes the antigen, two pathways can be distinguished:
a) The B-cell mediated pathway. It leads to the production of immunoglobulins against the hapten-carrier compound. A great variety of haptens and carriers have been shown to act this way. Many of the resulting antibodies are commercially available.
b) The T-cell mediated pathway. It leads to cytotoxic T-cell activity and to the recruitment of inflammatory cells. Usually, the carrier is a MHC molecule recognized by the T-cell receptor. In contact dermatitis, a well-resolved subgroup of this pathway, the haptens travel a long way with Langerhans cells before being checked by T cells in the lymphatic system.

 

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What kinds of haptens are known?

Haptens play a significant role in several processes:
a) Drug induced immune responses and allergies. Most drug molecules are too small to induce an immune response on their own.
b) Immune responses against endogenous compounds. Some rare but severe autoimmune diseases like lupus erythematosus are known, where metabolic compounds (e.g. phospholipids) act as haptens.
c) Allergies against xenobiotics. In a similar way as against drugs, allergies against many substances produced by foreign organisms can develop as soon as they reach the blood circuit.
d) Contact allergies. Known from frequent exposure of synthetic chemicals to skin, allergy-like symptoms such as irritation may arise. Besides organic compounds (skin sentisers), some metals like lead and nickel may cause similar symptoms. Practical research on potential skin sensitisers has great economic relevance to the hygiene industry.
e) Transition state analoga. These molecules have been tailored to resemble an activated state of a chemical reaction. Antibodies that an organism produces against these haptens under lab conditions have been demonstrated to be usable as catalytic antibodies.

 

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What are antibodies?

An antibody is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. This is because at the two tips of its "Y", it has structures akin to locks. Every lock only has one key, in this case, its own antigen. When the key is inserted into the lock, the antibody activates, tagging or neutralizing its target. The production of antibodies is called the humoral immune system.

 

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What data was compiled?

SuperHapten contains seven different sets of data
- 3D structures of haptenic compounds.
- names, synonyms and chemical grouping of haptens.
- physicochemical descriptors of haptens.
- antibodies that specifically bind haptens.
- information on carriers that present haptens for cells of the immune system.
- references to literature where haptenic compounds are mentioned.
- vendor information for both haptens and antibodies.

 

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Where do the structures originate?

All structures in SuperHapten were retrieved from major 2D chemical databases (NCI, CSD, whatever) using names found in the literature. They were used to generate 3D coordinates for the molecules with DSViewer.

 

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How were the haptens classified?

Two kinds of classifications were performed:
a) Terms describing the function of a compound (like antibiotics, pesticides, etc.) were identified and used to group 51% of the haptens.
b) All hapten structures were grouped automatically by 2D-structure matching. This resulted in 145 groups containing 5653 haptens. Each group was manually inspected and named.

 

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What are 'putative' and 'confirmed' haptens?

Haptens collected from literature and different web resources by keyword screening are called confirmed.
By structural screening, compounds with >= 90% Tanimoto coefficient were detected, this is the dataset of putative haptens.

 

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What are 'purchasable' and 'not available' haptens?

We have checked if the haptens are commercially obtainable and provide the ordering codes and external links to suppliers.

 

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What is the "Keyword Search"?

The keyword search allows you to search in about 7250 immunogenic compounds. It is also possible to search for a compound of interest by a variety of methods, like the name or the molecular weight. Most of the compounds are also searchable by their classification which can be selected from a pulldown menu. With this type of search you can find similar structures of known compounds, which are available by different suppliers.

 

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What is the "Structure Search"?

The search via marvin applet allows you to build your own structure and perform a similarity search in all haptens.It is also possible to load different molecular structure files into the applet and start a similarity search. With this type of search you can find similar structures, which are available by different suppliers.

 

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What is the "Similarity Search"?

The search for similar haptens allows you to search in the SuperHapten Database for 2D similar compounds.

 

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How can I perfom a 2D Similarity Search against the database?

Starting from a certain compound, the SuperHapten Database can be searched for similar molecules. A 2D similarity search is performed by calculating Tanimoto coefficients for the given molecule and the molecules in the database. After you have performed a compound- or template - search, simply click on the Search-Button in the "Similarity-Search" column of the search results table. You can also select how many hits you want to see.

 

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What are the System Requirements for MDLŽ Chime for MDLŽ Chime?

PC:

Software: for Chime 2.6 SP5

Windows XP with Microsoft Internet Explorer 6.0, and Netscape Communicator 4.75, 4.79 Windows 2000 with Microsoft Internet Explorer 6.0, 5.5 SP2, and Netscape Communicator 4.75, 4.79 Windows NT 4.0 with Micorsoft Internet Explorer 6.0, 5.5 SP2 and Netscape Communicator 4.75, 4.79

Hardware:

Pentium class recommended 64 MB or more recommended 800x 600 recommended


Macintosh:

Software:

Mac OS 9.0 with Netscape Communicator 4.75 Mac OS 8.6 with Netscape Communicator 4.75 Connectix RamDoubler is recommended if you have less than 32 MB of physical RAM. You need to increase the memory used by Netscape to 15000 K.

Hardware:

Power PC required 32 MB or more recommended 800 x 600 or better recommended

For more detailed information please visit MDLŽ Chime.

 

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