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Thiol Modifiers

Thiol modifiers are the common type of chemical modification for synthetic oligonucleotides (oligos). Thiol modifiers enable covalent attachment of oligonucleotides to a variety of biological molecules such as ligands, peptides or proteins, as well as solid supports. It is convenient to use them to prepare synthetic oligos for subsequent attachment chemistry. Creative Biolabs provides many types of thiol modifiers for custom oligonucleotide modification. Creative Biolabs’ experienced teams will meet our clients’ every specific requirement and expectation to promote their project development. Moreover, we are flexible to design the project based on clients’ special requirements and communicate with clients timely during the process of programs.


Thiol (SH) modifiers allow the covalent attachment of oligonucleotides to a variety of ligands or supports during or after solid-phase synthesis of DNA or RNA oligonucleotides. Thiol group can be linked to the 5’ or 3’ terminus of an oligo. Incorporation of reactive functional groups at specific sites among an oligo makes it possible to subsequently conjugate the oligo to a variety of ligands and surfaces. Thiol modified oligos will oxidize again over time, thereby the reduction procedure need to be repeated before coupling. Thiol modifiers are designed to react with a broad array of activated accepting groups, such as maleimide (Figure 1) and gold microspheres.

Thiol reacts with maleimide. Figure 1. Thiol reacts with maleimide. (Leiro, 2018)

Types of Thiol Modifiers Available at Creative Biolabs

C6 S-S oligos modified with the 5′ thiol modifier C6 S-S (Figure 2) are synthesized with an S-trityl-6-mercaptohexyl derivative protecting group attached. 5′ thiol modifier C6 S-S is one of the most frequently employed thiol modifications.

5’-Thiol modification. Figure 2. 5’-Thiol modification.

Thiol modifier with three or six atom spacers is usually used for the introduction of thiol modifiers on the 3’-end of oligonucleotides. For example, 3’-thiol modifier C3 S-S CPG is commonly used for the introduction of a thiol group to the 3’-terminal of the target oligonucleotide.

Dithiols or poly-thiols provide a higher level of stability and are therefore ideally suited for modifications of gold nanoparticles or surfaces.

Deoxythymidine (dT) modified with a spacer, and a thiol group can be used for adding internal thiol modifier groups at desired locations among oligonucleotide sequences.

Applications of Thiol Modified Oligos

Creative Biolabs aspires to become the trusted solution provider of your first choice. Our advanced technologies and highly experienced staffs are committed to advancing your program and reducing the overall development timeline. We have accumulated extensive experience in the synthesis of thiolated oligos. Our scientific experts are very happy to discuss your experimental design. If you have any special requirements for oligonucleotide synthesis with thiol modification, please don’t hesitate to contact us.


  1. Leiro, V.; et al. (2018). Conjugation chemistry principles and surface functionalization of nanomaterials. Biomedical Applications of Functionalized Nanomaterials. 35-66.

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