Bridged Nucleic Acids (BNA)
Bio-Synthesis offers small molecule conjugation and modification by covalently attaching
drugs, metabolites and labeled compounds with synthetic or natural polymers for
specific applications. Conjugation of these high affinity small molecules with biopolymers
provide a variety of biological functions such as cell signaling molecules, as tools
in molecular biology, as drugs in medicine, and in many other roles. Our experience
in small molecule synthesis, modification and conjugation includes but not limited
Our highly skilled chemists can carry out the synthesis of various complex intermediates,
scaffold, reference compounds and a wide range of research building blocks. All
custom small molecule synthesis and conjugation complexes are manufactured under
a strict quality control throughout the entire production cycles to minimize variations
and ensure superior QUALITY, higher RELIABILITY,
and CONSISTENCY in our products. At Bio-Synthesis, we strive with
competence and confidence to meet your demand for developing pre-clinical drug candidates
or innovative regents and tools efficiently and affordably. With our track record,
Bio-Synthesis is your ideal and reliable innovation partner in targeted drug discovery.
Biomolecules such as oligos and their analogs, peptide, peptidomimetics, antibody
fragments, enzymes, and other user-supplied biomolecules that have a functional
group can be used for conjugation. These biomolecules can be modified and linked
to one or several small molecules through homobifunctional or heterobifunctional
linkers via selective or non-selective covalent bond. Since choosing the correct
chemistry can sometimes seem overwhelming, it requires a careful understanding of
target molecule's structure and reactivity. These cross-linking and modifying agents
can be applied to alter the native state and function of peptides and protein; sugars
and polysaccharides; nucleic acids and oligonucleotides; lipids; and almost any
other imaginable molecule that can be chemically derivatized. Each conjugation project
assigned to Bio-Synthesis is carefully designed, modified and strategized. Bio-Synthesis
not only offers synthesis of biopolymers, but also assists clients who want to functionalize
or activate compounds ready to cross-link with pre-activated biomolecules, either
supplied by customers or prepared in-house. These pre-activated small molecules
can be created with an amine, acid, hydrazine, aldehyde/ketone, hydromxyamine, maleimide/alkylhalide,
and sulfhydryl functional group in a polymer. After conjugation of a biopolymer
with other biopolymers, a standard desalting, purification, quality check and final
concentration and labeling ratio are determined.
Non-commercial small molecule supplied by customer
User-supplied, non-commercial small or macromolecules should be sufficiently pure
(≥95% pure). Please provide the QC data (typically HPLC, MS, ESI or NMR data etc.)
and MSDS (if any) along with your compound. We can assist with the purification
and acquisition of analytical data. These compounds must contain functional groups
that can be targeted for cross-linking including carboxylate groups, primary amine
groups, aldehyde/keto residues, hydroxyl, hydrazine, hydrazide, aminoxy, saccharide
/glycan groups or thiol reactive functional group(s). Coupling also can be nonselective
using a photoreactive phenyl azide cross inker. If necessary, we can also assist
with the creation and activation of specific functionalities. Any sample supplied
by the client requires a quality check by our analytical team to ensure sample quality
Commercial available small molecules
Commercially available small molecules can be supplied by customers or ordered through
Bio-Synthesis. Common small molecules such as common fluorescent dyes, biotin-NHS
and other hetero-bifunctional cross-linkers are available at Bio-Synthesis. For
in stock compounds, Bio-Synthesis will charge customers only the amount needed for
conjugation. If the small molecules are to be purchased separately, the cost of
acquiring this material will be added to the invoice along with a $50 administration
charge per order.
Non-commercially available small molecules
We can custom synthesize small molecules either in house. A quotation will be prepared
for such syntheses.
Oligonucleotide, oligomimetics and custom gene or genomic DNA
DNA, RNA and nucleic acid analogs such as PNA can be synthesized in-house at Bio-Synthesis,
and then conjugated through amino, thiol, aldehyde, azide, carobxyl or 5'-phosphate
modification. Oligos supplied by the customer should be HPLC or gel purified (>90%
pure). Please provide the QC data needed for purity assessment. Extra charges may
apply for analyzing the starting materials at Bio-Synthesis.
Peptides, peptidomimetics, and expressed protein
Peptides or proteins can be synthesized or expressed in-house at Bio-Synthesis.
We label or conjugate peptides through N-terminal, C-terminal or internal side chain
of amino acids. Peptides supplied by the customer should be HPLC purified (>90%
pure) and should contain a single modification site. We can make any standard peptide
with functional groups incorporated through peptide synthesis. Please provide the
peptide sequence of the desired peptide on the order form.
Commercial antibodies can be supplied by customers or ordered through Bio-Synthesis
with an additional fee plus the cost of the antibody. Non-commercial biopolymers
supplied by customers should be affinity purified. Please provide gel electrophoresis
data along with your antibody. Bio-Synthesis also assists customers with antibody
production, purification, modification, fragmentation prior to any cross linking
We offer post-synthetic modification of ligands to be immobilized on various solid
supports, which allow the immobilization process to occur selectively in the presence
of common functional groups, including amines, thiols, carboxylic acids, and alcohols.
Bio-Synthesis offer functional group modification and deravitization;
See more information on Biomolecule Modification
Every chemical modification or conjugation process involves the reaction of one
functional group with another, resulting in the formation of a covalent bond. The
creation of bioconjugate reagents with spontaneously reactive, or selectively reactive
functional groups, forms the basis for simple and reproducible cross-linking or
tagging of target molecules. Our well-trained chemists assist clients from starting
project scope collections to design, and determine appropriate homobiofunctional
or heterobifunctional cross-linking chemistries. We have delivered thousands of
custom conjugated biopolymers and are fully capable of meeting the ever-increasing
bioconjugation needs in biological and drug discovery research. Hundreds of reaction
systems have applied in our organic laboratories.
Price varies based on the project specifications. Price
does not include the cost of small molecule or biopolymer which is required to be
supplied by the customer or ordered through Bio-Synthesis from a commercial vendor.
Some of the small molecules are commercially available in an activated form. For
non-active molecules, Bio-Synthesis can assist with the design and, if deemed necessary,
biopolymer modification to introduce additional functional groups and extra
linkers. Please contact us for a quote.
Using preactivated small molecule and biomolecule with
chemical reactive groups such as amine, thiol, carboxylate, hydroxyl, aldehyde and
ketone, active hydrogen, photo-chemial and cycloadition reactions and cross link
via zero-length , homobifunctional, heterobiofunctional or multi-functional cross-linking
chemistries, denrimer and dendrons, cleavable regent system.
After standard desalting, or purification,
a small percent of heterogeneous products containing single or multi-site conjugate
per molecule may exist.
All custom synthesis of biopolymer, modification or
bioconjugation of small molecule services are manufactured under strict quality
control processes. Analytical HPLC and MS analyses are performed in every development
cycle. Final target conjugates must first be isolated from excess or unreacted reagent.
In many cases, simple dialysis may suffice to remove unreacted reagent from the
reaction solution. Depending on the project scope, size-exclusion chromatography
(SEC), HPLC, may also be used to either remove excess reagent or isolate and characterized
the cross-linked product. Cross-linked target molecules may then be further characterized
by biochemical or biophysical techniques. Once the product has been purified, it
may be subject to many different types of studies including spectroscopic (MALDI-top,
ESI, LC-MS Fluorescence), electrophoresis, immunochemical biochemical, enzymatical
analysis. QC (quality control) and QA (quality assurance) procedures are also followed
independently to offer you double guarantee for the highest quality possible of
every delivered conjugates. Moreover, our dedicated technical account managers will
guide your project through every step of the process and constantly keep you informed
of the latest project progress.
The typical delivery consisted of lyophilized
sample in individual fully labeled vials, shipment also contain COA, MS, HPLC and/or
other analytical data. Additional analytical data also available upon request.
Visit our literature vaults for more references and citings.
For us to better understand your customized project, please complete our Bioconjugation Service Questionnaire. The more our chemists understand your project needs, the more accurate feedback we will be able to provide you. Provide us with your project details will enable to us to recommend the best reagents to use for your project. The most useful and readily available tools for bioconjugation projects are cross-linking reagents. A large number of cross-linkers, also known as bifunctional reagents, have been developed. There are several ways to classify the cross-linkers, such as the type of reactive group, hydrophobicity or hydrophilicity, and the length of the spacer between reactive groups. Other factors to consider are whether the two reactive groups are the same or different (for example, heterobifunctional or homobifunctional reagents), whether the spacer is cleavable, and whether the reagents are membrane permeable or impermeable. The most accessible and abundant reactive groups in proteins are the ϵ-amino groups of lysine. Therefore, a large number of the most common cross-linkers are amino selective reagents, such as imidoesters, sulfo-N-hydroxysuccinimide esters, and N-hydroxysuccinimide esters. Due to the high reactivity of the thiol group with N-ethylmaleimide, iodoacetate and a-halocarbonyl compounds, new cross-linkers have been developed that contain maleimide and a-carbonyl moieties. Usually, N-alkylmaleimides aremore stable than their N-aryl counterparts.
In addition to the reactive groups on the cross-linkers, a wide variety of connectors and spacer arms have also been developed. The nature and length of the spacer arm play an important role in the functionality. Longer spacer arms are generally more effective when coupling large proteins or those with sterically protected reactive side-chains. Other important considerations are the hydrophobicity, hydrophilicity, and the conformational flexibility. Long aliphatic chains generally fold on themselves when in an aqueous environment, which makes the actual distance spanned by such linker arms less than expected. Instead, spacers that contain more rigid structures (for example, aromatic groups or cycloalkanes) should be used. These structures, however, tend to be very hydrophobic which could significantly decrease the solubility of the modified molecules or even modify some of their properties. In such cases, it is recommended to choose a spacer that contains an alkylether (PEO) chain. Bio-Synthesis offers several cross-linkers with PEO chains, such as thiol-binding homobifunctional reagents, heterobifunctional based, and their derivatives.
Within 3-5 days upon receiving your project scope, we will provide you an appropriate quotation. An order can be placed with PO (Purchase Order) or major credit cards ( ). Your credit card will be billed under Bio-Synthesis, Inc.