Custom Monomers or Building Blocks

Libraries of custom amino acids, nucleotides, and chemical fragments are managed through the Vault-level monomer management workflow. You can now create monomers centrally within a Vault and share them with selected users, unlocking several key benefits:

• Enhanced collaboration – Easily share monomers across teams to ensure everyone works with the same building blocks and custom identifiers
• Improved consistency – Standardize designs by using centrally managed monomers
• Better searchability – Quickly find and reuse monomers within a growing library
• Increased efficiency – Reduce duplication of effort by avoiding repeated creation of the same monomers
• Accurate molecular definition – Atom- and bond-level information is defined, enabling precise molecular weight calculation for modified Peptides and Oligos
• Auto-recognition and auto-correction (upcoming feature) – Minimize errors and streamline the design process with intelligent system support

These improvements expand the scope of what’s possible, making it easier to design, manage, and collaborate on complex modified biologics.

We’ll walk through how to create a new monomer and take full advantage of these powerful capabilities.

How to create a single new monomer:

1. Create a new molecule (We recommend registering monomers under a dedicated project named “Monomer” within the Vault)

2. Either paste SMILE/MOL file or Launch the Structure Editor to draw the structure using drawing canvas

3. Now, click Create Monomer from the left panel. The system should automatically detect the components and attachment points.

   

4. Provide the required details:
   • Monomer Type (Peptide/Nucleotide/Fragment)
   • Monomer code (these are the codes used in sequences, represented by enclosing them in square brackets.
   • Natural analogue if applicable.
5. If needed, click Edit from this pop-up window to correct them in the structure editing canvas.
6. Adjust the structure orientation and ensure there are no error messages, then click Apply.

How to create bulk monomers:

1. Upload the file from the “Import Data” tab in the top blue banner.

   

2. Select the option “Compose monomers from columns” and click “Update.”

   

3. The system will automatically recognize the SDF and, in most cases, generate monomers with the correct attachment points. If not, you will have the opportunity to edit the monomers after registration.

4. You can also adjust the orientation of monomer coordinates in this window. Options are available to apply deprotection for amines and acids instantly. 

5. Options are available to apply deprotection for amines and acids instantly. 

   Note: Deprotection option automatically converts protected functional groups into their reactive forms. For example, amines (e.g., Boc- or Fmoc-protected) are converted to free –NH₂, and acids (e.g., ester-protected) to free –COOH, ensuring monomers are ready for accurate registration and downstream use.

6. Fragment types can be selected manually, but for mixed files, then choose "Any" and the system will automatically assign them to the appropriate category.

   

7. Now hit "Process File" to register the monomers at Vault

8. The assigned monomer codes can be used within sequences when you register them. For example: AHTSGS[Cpg]HTS, where [Cpg] represents the custom monomer code for cyclopropylglycine.

How to edit existing monomer:

To change the attachment point for a monomer such as gamma glutamic acid, please first navigate to the Molecule page, where you will find the option to define a custom monomer.

Delete and recreate Monomer-

1. Click Edit under the Custom Monomer Library

   

2. In the pop-up window, remove the existing monomer information and confirm the deletion of the monomer.

3. Now click Edit for main structure, then select “Launch the Structure Editor” 

   

   

4. Modify the structure as needed:
   • Rearrange attachment points
   • Make any required structural changes
5. Click the green icon (“Use this structure”) in the bottom-right corner and save your changes for this structure
6. Now, click Create Monomer from the left panel (See attached image 4). The system should automatically detect the components and attachment points.
   • If needed, click Edit in the pop-up window to adjust them.

7. Provide the required details:

   • Monomer code
   • Natural analogue
   • Structure orientation

   Ensure there are no error messages, then click Apply.

How to edit attachment points for monomer

There is an alternative way to define the desired attachment points. Its by recreating the new molecule.

1. First, create a new molecule by pasting a SMILES/MOL file or using the structure editing tool.

2. In the structure editing canvas, define attachment points by selecting R1/R2 from the left toolbar and then clicking on the desired atom.

   

3. Once R1/R2 are defined, click “Create a Monomer” (or use Ctrl+M) from the left panel and fill up monomer attributes

   

   • Select the monomer type from the dropdown
   • Provide a symbol for the monomer code, along with the name and natural analogue.
   • Double-check the attachment points here, as they are set by default with hydrogen as leaving groups.

4. Click submit to register the monomer in the Vault.

   

5. Finally, register the molecule. Note that this approach bypasses the auto-recognition of monomer attachment points and is only available via the single monomer registration page.

How to find library of monomers:

Currently, searching monomers directly by their codes is not supported (this feature is a work in progress). However, if the code is added in the synonym field, you can search for monomers using a simple query with the code.

In the report table, the column labeled “Monomer” under the Molecule field will display the monomer structure, including all attachment points, leaving groups, type, code, and natural analog.