High Quality Antisense-Peptide Bioconjugation Services
All of our oligomimetic antisense-peptide conjugates includes: synthesis and modification of oligo and peptide, careful monitoring for sequence integrity and systematic control by PAGE or mass spectrometry analysis before and after conjugation. All conjugates are purified by HPLC, quantified by UV absorbance at 260 nm, validated by mass spectrometry and delivered lyophilized within 2-3 weeks.
We also provide labeled peptide-antisense oligo conjugates and many other modifications to meet your specific needs!
Price
The price varies depending on different methods used in obtaining peptide-oligo conjugate. Please contact us for a quotation.
Chemistry
Methods in preparing peptide-oligo conjugates in our laboratory are:post-synthetic conjugation (or post-assembly conjugation, fragment coupling strategy),total stepwise synthesis (or on-line solidphase synthesis), native ligation and template-directed ligation.
The 5', internal or 3'-terminus of an oligo can be covalently linked to N-, internal or C-terminus of a peptide or other delivery vehicles such as peptide using a preactivated small molecule, with functional groups residing in peptides and oligos that have amine, thiol, carboxylate, hydroxyl, aldehyde, ketone, active hydrogen and alkyne/azide for cycloaddition reactions or cross-linking with one another (through variety of conjugation chemistries that include either stable or cleavable linkage). Although, the price for using other strategies for making peptide-oligo conjugate is the same, the price for obtaining other modified peptides, oligos and cross-linkers includes either stable or cleavable linkages (or higher additional spacers).
Example of using NHS ester-maleimide mediated conjugation chemistry where n-terminal Cys incorporated peptide to react with a maleimide activated oligo. If the peptide
has an internal Cys, we can use other strategies such as oxime formation through a hydroxyl-amine modified peptide reaction with an aldehyde modified oligo. Although,the price for using other strategies for making peptide-oligo conjugate is the same,the price for obtaining other modified peptides, RNA oligo, or different cross-linking chemistries that include either stable or cleavable linkages, additional spacer may be higher.
Specification
Product is HPLC purified and usually over 85-95% pure
Procedure
Functionalization of oligo is manufactured under strict quality control processes. Analytical HPLC and MS analyses are performed in every development cycle. Depending on type of conjugation chemistry we use, buffer exchange (if necessary) conjugates undergo gel filtration or use of the centrifugal concentrator to remove excess cross-linking reagents and oligonucleotides. Then, either size-exclusion chromatography (SEC) or reverse phase HPLC may also be used to either remove excess reagents or isolate and characterize the cross-linked product. Once the product has been purified, it may be subject to many different types of studies including spectroscopic (MALDI-TOF, ESI, LC-MS Fluorescence) electrophoresis.
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 conjugate. Final quantity is systematically validated by UV absorbance at 260 nm. 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.
Delivery Specifications
The typical delivery consists of lyophilized sample in individual fully labeled vials.The shipment also contains COA, MS, HPLC and/or other analytical data. Additional analytical data is also available upon request.
Contact our Technical Service Center at 800.227.0627 or contact us online with your detailed oligo-peptide project specifications, a project manager will be
assigned to help you with design and develop an appropriate synthetic method for your specific needs.
Ordering and Submitting Requests for Bioconjugation Services
For us to better understand your customized project, please complete our Bioconjugation Service Questionnaire. The more our chemists understand your project’s needs, the more accurate your provided feedback will be. Providing us with your project’s details enables 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 (i.e. heterobifunctional or homobifunctional reagents), spacer is cleavable and if 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 containing maleimide and a-carbonyl moieties. Usually, N-alkylmaleimides are more 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, making the actual distance spanned by such linker arms less than expected. Instead, spacers containing 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 alkyl ether (PEO) chain. Bio-Synthesis offers several cross-linkers with PEO chains, such as thiol-binding homobifunctional reagents, heterobifunctional bases 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.