siRNA-Conjugated Peptide Synthesis

siRNA is considered an effective therapeutic agent due to its high specificity and efficiency in inhibiting overexpressed genes during disease progression. Due to their structural and functional diversity, peptides are emerging candidate nanocarriers for siRNA delivery. CD Formulation can provide high-quality siRNA-peptide conjugates as well as custom synthesis and conjugation services.

What is siRNA?

siRNA is a molecule that expertly stifles gene expression with a delicate touch. Generally speaking, siRNA is double-stranded and very short, with a length of 20 to 25 nucleotides. In the double strand, one strand is called the guide strand and the other strand is called the passenger strand, also known as the sense strand and the antisense strand, respectively. A distinctive hallmark of this intricate molecule is its charmingly elusive 3' OH dinucleotide overhang. When a peptide is conjugated to siRNA, the conjugate uses the peptide as a nucleic acid carrier to bring the short siRNA into the body to exert its gene-silencing effect and specifically silence the expression of the target gene to achieve therapeutic purposes.

Fig. 1 The structure of siRNA. (CD Formulation)

Explore Our Custom siRNA-Conjugated Peptide Synthesis Services

CD Formulation offers the following two custom synthesis options for peptides and siRNA, but we are happy to discuss conjugation projects using your own siRNA or peptide.

• Single-stranded siRNA-peptide conjugates.
• Double-stranded siRNA-peptide conjugates.

Double-stranded siRNA is generally stable enough to be used without modification but often requires extensive modification with nucleoside analogs for in vivo use.

Our siRNA and peptide conjugate are manufactured under strict quality control processes. Analytical HPLC and MS analyses are performed at each development cycle. Depending on the type of conjugation chemistry we use, the siRNA-conjugated peptides are subjected to gel filtration to remove excess cross-linking reagents and oligonucleotide purification. They are then separated and characterized by size exclusion chromatography (SEC) or reversed-phase HPLC.

Our siRNA-Peptide Conjugation Strategies

siRNA-Conjugated Peptide Conjugation

Fig.2 Schematic diagram of siRNA and peptide conjugation. (CD Formulation)

The N-terminus or the C-terminus, alongside the convoluted interior landscape, emerge as preferred locales for anchoring to either the 5' or 3' extremities of the siRNA oligonucleotide. The most common connection options are:

• N-terminal linkage: The peptide intertwines with the 5' extremity of the siRNA via its N-terminus, an intricate dance of molecular connectivity. This sophisticated methodology typically harnesses the amino group of the amino acid, forging a bond with the phosphate moiety of the nucleic acid strand.
• C-terminal linkage: The C-terminus of the peptide can be linked to the 3' end of the siRNA, often using a carboxyl group to link with the phosphate group of the nucleic acid.
• Internal linkage: The peptide can be linked to the siRNA at any position within it. This situation usually requires special chemical modification and design to ensure the stability and functionality of the linkage.

In the different attachment options mentioned above, siRNA oligonucleotides can be cross-linked through different chemical reactions, such as reactions of functional groups such as amino, thiol, carboxylic acid, hydroxyl, aldehyde, and ketone. These cross-links can be formed by stable chemical bonds or achieved through cleavable linkages.

siRNA-Conjugated Peptide Modification

Modifications can be incorporated into the siRNA or peptide molecules, or both molecules (if appropriate). Modifications include:

• Phosphorothioate bonds on the backbone of the siRNA molecule.
• Modified bases on the siRNA.
• Modified amino acids incorporated into the peptide sequence.
• Fluorescent and dye labels, including but not limited to FAM, TAMRA, BHQ1, and BHQ2.
• Biotinylation
• Spacers

Delivery Specifications of siRNA-Conjugated Peptide

Peptide Manufacturing & Analytical Services

In addition to peptide synthesis capabilities, CD Formulation combines flexible GMP manufacturing facilities with cutting-edge peptide analytical knowledge to provide a full range of quality control testing services to accelerate the commercialization of your products, including:

Publication

CD Formulation is a trusted partner for peptide synthesis. Please don't hesitate to contact us if you are considering using siRNA-conjugated peptides in your project. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.