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Custom Synthesis

Explore Our Custom Synthesis

With our extensive knowledge of mRNA and oligonucleotide chemistry, we can design and develop new molecules to meet customers' needs.

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We offer customized synthesis for all series of our building blocks.

Custom Synthesis for Raw Materials

  • Nucleosides

    General structures for Nucleosides

    Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (either ribose or deoxyribose), whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine and inosine.

    Normal/modified Nucleosides

    B = Base (A, C, G, U, T, I, X, pU, iso-C, iso-G)
    P = Null, Me, F, Cl, Br, I, NH2, isotope, deaza, thio, etc.
    X/Y = H, OH, F, OTBDMS, OMe, OMOE, O-Propargyl, NH2, N3, etc.

    Arabino Nucleosides

    B = Base (A, C, G, U, I, T)
    P = Null, Me, F, NH2, etc.
    X = OH, F

    2'-O-4'-C-Locked Nucleosides

    B = Base (A, C, G, U, T, etc.)
    X = OH, NH2, etc.

  • Protected Nucleosides

    General structures for Protected Nucleosides

    Primary amine groups of nucleosidic bases covered by standard and labile protection groups.

    Base Protected Nucleosides

    B = Base (A, C, G, etc.)
    P = Me, Ac, Bz, dmf, iBu, PhAc, Pac, Tac, etc.
    X/Y = H, OH, F, OTBDMS, OMe, OMOE, O-Propargyl, NH2, etc.

    DMT Protected Nucleosides

    B = Base (A, C, G, U, I, T, etc.)
    P = Null, Me, halogen, Ac, Bz, dmf, iBu, PhAc, Pac, Tac, etc.
    X/Y = H, OH, F, OTBDMS, OMe, OMOE, O-Propargyl, NH2, etc.

    TIPDS Protected Nucleosides

    B = Base (A, C, G, U, T, pU, T, iso-C, etc.)
    P = Null, Ac, Bz, dmf, iBu, PhAc, Pac, Tac, isotope, etc.
    X = OH, OMe, F, OMOE, etc.

    PMO Nucleosides

    B = Base (A, C, G, T, U)
    P = Ac, Bz, dmf, iBu, PhAc, Pac, Tac, etc.

    DMT/Base Protected 2'-O-4'-C-Locked Nucleosides

    B = Base (A, C, G, U, T, etc.)
    P = Null, Ac, Bz, dmf, iBu, PhAc, Pac, Tac, etc.
    X = OH, ODMT.

  • Nucleotides

    General structures for Nucleotides

    Nucleotides are molecules consisting of a nucleoside and a phosphate group. They are the basic building blocks of DNA and RNA.

    They are organic molecules that serve as the monomer units for forming the nucleic acid polymers deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are the building blocks of nucleic acids; they are composed of three sub unit molecules: a nitrogenous base (also known as nucleobase), a five-carbon sugar (ribose or deoxyribose), and at least one phosphate group.

     

    Nucleotides also play a central role in metabolism at a fundamental, cellular level. They carry packets of chemical energy—in the form of the nucleoside triphosphates Adenosine triphosphate (ATP), Guanosine triphosphate (GTP), Cytidine triphosphate (CTP) and Uridine triphosphate (UTP)—throughout the cell to the many cellular functions that demand energy, which include: synthesizing amino acids, proteins and cell membranes and parts, moving the cell and moving cell parts (both internally and intercellularly), dividing the cell, . In addition, nucleotides participate in cell signaling (cyclic guanosine monophosphate or cGMP and cyclic adenosine monophosphate or cAMP), and are incorporated into important cofactors of enzymatic reactions (e.g. coenzyme A, FAD, FMN, NAD, and NADP+).

     

    In experimental biochemistry, nucleotides can be radiolabeled with radionuclides to yield radionucleotides.


    B = Base (A, C, G, T, U, pU, I, iso-G)
    Salt type = H, Na, Li, K, NH4, TEA, tris, etc.
    Custom for concentration & salt type are available.

    NTP/dNTP

    X = H, OH

    NDP/dNDP

    X = H, OH

    NMP/dNMP

    X = H, OH

    NP4/dNP4

    X = H, OH

    Modified Nucleotides

    P = Null, Me, OMe, halogen, etc.
    X/Y = H, OH, F, OMe, etc.
    Z = MP, DP, TP, IM, etc.

    CDN (Cyclic Dinucleotides)

    A1, A2 = Nucleic base/nucleic base analogue
    X1YZ2, X2Y'Z1 = OP(O)2O- or else
    R1, R2 = H, OH, O-side chain or F, etc.
    Custom synthesis available, Purity ≥ 95%

    Arabino Nucleotides

    B = Base (A, C, etc.)
    P = Null, F, etc.

    Cap Analog

    B = A or G or m7G, a linker can be attached to the base
    R = OH or OMe
    X = O or S
    n = 0 or 1

  • Phosphoramidites

    General structures for Phosphoramidites

    A phosphoramidite (RO)2PNR2 is a monoamide of a phosphite diester. The key feature of phosphoramidites is their markedly high reactivity towards nucleophiles catalyzed by weak acids e.c., triethylammonium chloride or 1H-tetrazole. In these reactions, the incoming nucleophile replaces the NR2 moiety.

     

    Our nucleoside phosphoramidites are produced and packaged to ensure the highest performance on commercial oligonucleotide synthesizers. Every batch is accompanied by COA and Spec., showing the results of our QC testing.

    Normal/modified Phosphoramidites

    B = Base (A, C, G, U, pU, I, T, abasic)
    P = Null, Me, NH2, Ac, Bz, dmf, iBu, PhAc, Pac, Tac, etc.
    X = H, F, OTBDMS, OMe, OMOE, O-Propargyl, etc.

    2'-O-4'-C-Locked Phosphoramidites

    B = Base (A, C, G, U, T)
    P = Null, Ac, Bz, dmf, iBu, PhAc, Pac, Tac, etc.

    FANA Phosphoramidites

    B = Base (A, C, G, U)
    P = Null, Ac, Bz, iBu, etc.

    PMO Phosphoramidites

    B = Base (A, C, G, T)
    P = Null, Bz, Ac, iBu, dmf, PhAc, Pac, Tac, etc.

    3'-TrNH Phosphoramidites

    B = Base (A, C, G, T)
    P = Null, Ac, Bz, dmf, iBu, etc.

    Linker Phosphoramidites

    P = DMT, MMT, Tr, TFA, etc.

  • Succinates

    General structures for Nucleoside Succinates

    In oligonucleotide synthesis, succinates are used to derivatize the solid support onto which the oligonucleotides are built. This derivatization process creates a linker arm between the solid support and the first nucleotide of the oligonucleotide. The linker arm serves two purposes:

     

    • Attachment of the first nucleotide: The linker arm provides a functional group that the first nucleotide can be chemically attached to, initiating the oligonucleotide chain.

     

    • Cleavage of the final oligonucleotide: After synthesis is complete, the linker arm contains a chemical cleavage site that allows the final oligonucleotide to be released from the solid support.

    Normal/modified Succinate

    B = Base (A, C, G, U, T, Abasic)
    P = Null, Ac, Bz, iBu, dmf, etc.
    X = H, F, OMe, OTBDMS, OMOE, etc.

  • GalNAc

    General structures for GalNAc

    GalNAc, short for N-Acetylgalactosamine, finds its application in targeted drug delivery, particularly for the liver. Here's how it works:

     

    Target: GalNAc targets the Asialoglycoprotein Receptor (ASGPR) on liver cells. ASGPR is abundant and specifically recognizes GalNAc molecules.

     

    Conjugation: GalNAc is attached to therapeutic molecules, such as siRNA (small interfering RNA) or antisense oligonucleotides (ASOs). These therapeutic molecules need a delivery system to reach their target site in the body.

     

    Delivery: When the GalNAc-conjugated molecule is injected into the bloodstream, the GalNAc moiety acts like a key that unlocks the ASGPR on liver cells. This specific interaction allows the therapeutic molecule to be efficiently delivered into the liver cells.

    GalNAc

  • Dyes & Quenchers

    Our dye product line include biotin, Cyanine series, FAM, TAMRA, HEX, TET, etc.

     

    Fluorescein labelled oligonucleotides have found applications in DNA sequencing and amplification, as well as techniques for genetic analysis. In the forefront of this development has been current fluorescein phosphoramidite.

     

    Fluorescent–labeled phosphoramidites feature absorption and emission spectra suitable for a broad range of applications, including microscopy and PCR. These phosphoramidites may be used on all automated DNA synthesizers using standard synthesis procedures.

     

    A dark quencher (also known as a dark sucker) is a substance that absorbs excitation energy from a fluorophore and dissipates the energy as heat; while a typical (fluorescent) quencher re-emits much of this energy as light. Dark quenchers are used in molecular biology in conjunction with fluorophores. When the two are close together, such as in a molecule or protein, the fluorophore's emission is suppressed. This effect can be used to study molecular geometry and motion.

  • Cyclic Nucleotides (CDNs)

    General structures for Cyclic Nucleotides (CDNs)

    CDNs' applications in oligo synthesis:

     

    Modulation of enzymatic activity: Certain enzymes involved in oligonucleotide synthesis, such as kinases and phosphatases, can be regulated by CDNs. By controlling the activity of these enzymes, researchers can potentially influence the efficiency and fidelity of the synthesis process.

     

    Development of novel oligonucleotide analogs: The cyclic structure and unique properties of CDNs can inspire the design of novel oligonucleotide analogs. These analogs could possess improved properties like enhanced stability against degradation or specific binding affinities.

    Customized CDNs 3’-5’

    A1, A2 = Nucleic base/nucleic base analogue
    X1YZ2, X2Y'Z1 = OP(O)2O- or else
    R1, R2 = H, OH, O-side chain or F, etc.

     

    Custom synthesis available, Purity ≥ 95%

    Customized CDNs 5’-5’

    A1, A2 = Nucleic base/nucleic base analogue
    X1YZ2, X2Y'Z1 = OP(O)2O- or else
    R1, R2 = H, OH, O-side chain or F, etc.

     

    Custom synthesis available, Purity ≥ 95%

  • Dinucleosides phosphate

    General structures for Dinucleosides phosphate

    Dinucleoside Phosphates: A Niche Application in Oligonucleotide Synthesis

     

    While the phosphoramidite approach reigns supreme in solid-phase oligonucleotide synthesis, dinucleoside phosphates offer a specialized yet valuable strategy for constructing short oligonucleotides in solution.

     

    The H-Phosphonate Approach and Dinucleoside Building Blocks

     

    The utility of dinucleoside phosphates lies within the H-phosphonate approach, an alternative to the dominant phosphoramidite methodology. This approach leverages dinucleoside H-phosphonates, which possess a phosphate group bridging two nucleoside units, as the fundamental building blocks. Subsequent condensation of these dinucleoside H-phosphonates with additional nucleosides facilitates the construction of longer oligonucleotides.

    Customized Dinucleosides phosphate

    B = Nucleic base/nucleic base analogue
    R = OH, OMe, OMOE, etc.

  • Dimer Phosphoramidites

    General structures for Dimer Phosphoramidites

    Dimer phosphoramidites offer a unique advantage in oligo synthesis, particularly for RNA oligonucleotides. Here's how they are applied:

     

    Faster and More Efficient Synthesis:  Regular oligonucleotide synthesis involves coupling individual nucleotide phosphoramidites one by one to build the desired sequence. Dimer phosphoramidites, as the name suggests, contain two pre-linked nucleotides. Incorporating these dimers into the synthesis process reduces the number of coupling steps required, significantly speeding up the process.

     

    Improved Purity and Yield: Especially for RNA oligonucleotides, traditional single nucleotide coupling can lead to lower purities and yields due to the presence of a 2'- hydroxyl group. Dimer phosphoramidites can help address this challenge. By incorporating pre-linked dinucleotide units, the chance of side reactions and errors during each coupling step is reduced, potentially resulting in higher purity and yield of the final RNA product.

     

    Applications in siRNA Synthesis: Short interfering RNA (siRNA) molecules are a type of RNA used to silence specific genes. Dimer phosphoramidites have proven valuable in synthesizing siRNA. By incorporating pre-formed dinucleotide blocks, researchers can achieve better control over the final structure and improve the purity of siRNA molecules.

    Customized Dimer Phosphoramidites

    B = Nucleic base/nucleic base analogue
    X = O or S

  • Trimer Phosphoramidites

    General structures for Trimer Phosphoramidites

    Trimer phosphoramidites are powerful tools in oligonucleotide synthesis, particularly for applications involving mutagenesis, which is the process of introducing specific changes to a DNA sequence. Here's how they come into play:

     

    Regular Oligo Synthesis vs. Trimer Phosphoramidites:

     

    Typically, oligos are built one nucleotide (single building block) at a time. This can lead to issues like:

     

    Codon Bias: Not all codons (triplets of nucleotides specifying an amino acid) are created equal. Traditional synthesis might favor incorporating certain nucleotides more frequently, skewing the final protein product.

     

    Frame-Shift Mutations: Errors during synthesis can insert or delete extra nucleotides, causing the entire reading frame of the translated protein to shift.

     

    Stop Codons: Mistakes can introduce stop codons prematurely, leading to truncated, non-functional proteins.

     

    Trimer phosphoramidites are pre-assembled units containing three linked nucleotides, essentially representing a codon. Their use offers several advantages:

     

    Codon-Based Mutagenesis: By incorporating pre-defined codons, trimer phosphoramidites ensure the desired amino acid is incorporated, reducing codon bias and improving accuracy.

     

    Reduced Frame-Shift Errors: Since three nucleotides are added as a single unit, the chance of insertion/deletion errors is minimized, leading to higher fidelity sequences.

     

    Minimizes Stop Codons: The pre-defined nature of trimers reduces the risk of accidentally incorporating stop codons during synthesis.


    Overall, trimer phosphoramidites offer a more precise and controlled approach to oligo synthesis, particularly for generating libraries of mutated genes for protein engineering or functional studies.

    Customized Trimer Phosphoramidites

    B = Nucleic base/nucleic base analogue
    X = O or S

Contact our experts to discuss your needs.