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As siRNA interference has been successful in gene silencing application, the major
limitation in utilizing siRNA for therapeutic applications is the inability far large anionic molecules to diffuse across cellular membrane. While intracellular
delivery of these siRNA oligomers has been the focus of a large number of research
groups worldwide, chemical conjugation of siRNA to cationic peptide CPP (cell-penetrating
peptides) or penetrating, has provides an interesting approach for enhancing delivery
of antisense and siRNA to cells and tissues.
Bio-Synthesis provides synthesis and conjugation of siRNA to peptide in high quality
and yields. Peptide-siRNA complexes produced in our state-of-the-art chemical biology
facilities and expertise in cross-linking chemistries. Each conjugate is meticulously
monitored during synthesis and controlled according to Bio-Synthesis stringent
quality assurance and quality control standards. The final product is identified
by mass spectrum and purity is analyzed gel electrophoresis. As always, quality
All of Bio-Synthesis's siRNA-peptide conjugates include: synthesis and modification of siRNA and peptide, conjugation, and each biopolymer is carefully monitor for
its sequence integrity and systematically controlled by PAGE or mass spectrometry analysis. Quantity is validated by UV absorbance at 260 nm.
Specification of siRNA-Peptide Conjugates
The price varies depending on different methods used in obtaining peptide-oligo conjugate. Please contact us for a quotation.
Double-stranded siRNA is generally sufficiently stable in cell culture to be used
without modification, but are usually heavily modified with nucleoside analogs for in vivo use. 5', internal or 3'-terminus of an siRNA oligos can be covalently linked to N-, internal or C-terminus of a peptide using preactivated small molecule with functional group residing in peptide. Oligos such as amine, thiol, carboxylate,hydroxyl, aldehyde and ketone, active hydrogen, photo-chemical and cycloaddition reactions and crosslinking with one another through variety of different 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, oligo and cross linker includes either stable or cleavable linkages, or additional spacer may be higher.
Product is HPLC purified and usually over 85-95% pure
Functionalization of oligos and peptides are manufactured under strict quality control process. Analytical HPLC and MS analyses are performed in every development cycles.
Depending on the type of conjugation chemistry we use, after buffer exchange (if necessary)
conjugates undergo gel filtration or through use of the centrifugal concentrator to remove excess crosslinking reagents and oligonucleotides. Then by either size-exclusion chromatography (SEC), reverse phase HPLC, may also be used to either remove excess reagent or isolate and characterized 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), and 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
conjugates. 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.
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.
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.