Description

Phthalimidooxy-dPEG®12-NHS ester, product number QBD-10011, is a protected aminooxy compound linked to an amine-reactive N-hydroxysuccinimidyl (NHS) ester through a medium-length (41 atoms, 46.3 Å), single molecular weight, discrete polyethylene glycol (dPEG®) spacer. This allows a hydrophilic, protected aminooxy group to be installed on peptides, proteins, small molecules, and amine-functionalized surfaces.

The phthaloyl moiety on phthalimidooxy-dPEG®4-NHS ester stably protects the aminooxy group. Following amide bond formation, the phthalimide group can be removed using aqueous hydrazine or hydroxylamine, leaving the aminooxy group free to react. Oxime bonds form from the reaction between an aminooxy group and an aldehyde (creating an aldoxime bond) or ketone (creating a ketoxime bond). Compared to hydrazone bonds, oxime bonds are exceptionally stable. They do not break under physiological or even slightly acidic conditions that can occur under some physiological states.

The amine-reactive NHS ester has optimal reactivity in the pH range of 7.0 – 7.4. This group should be reacted first as the subsequent deprotection step for the aminooxy group will also react with the NHS ester.

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Description

Fmoc-N-amido-dPEG®12-NHS ester, product number QBD-10996 contains an Fmoc-protected amine on one end of a medium-length (40 atoms), single molecular weight, discrete-chain-length polyethylene glycol (dPEG®) spacer and the N-hydroxysuccinimidyl (NHS) ester of a propionic acid group on the other end. This product is ready for the direct introduction of a water-soluble, amphiphilic spacer into a peptide chain without the need to activate the carboxylic acid moiety. The Fmoc protecting group on the N-terminus of the molecule cleaves easily with standard peptide chemistry.

Fmoc-N-amido-dPEG®12-NHS ester permits our customers to insert a dPEG® spacer into a peptide chain using solid-phase or solution-phase chemistry. The spacer attaches at the N-terminal end of the peptide chain or on the free amine side chain of amino acids such as lysine. Additional peptide synthesis can be carried out to extend the peptide further, creating a peptide with a flexible, hydrophilic linker or spacer in the middle. Also, the dPEG® compound can provide spacing in a synthetic construct where steric hindrance is a problem. Amphiphilic, non-immunogenic dPEG® increases the hydrodynamic volume and improves the water solubility of the peptide while remaining soluble in organic solvents. The Fmoc protecting group is removed easily with a solution of piperidine in N,N-dimethylformamide (DMF).

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Design of a modular tetrameric scaffold for the synthesis of membrane-localized D-peptide inhibitors of HIV-1 entry. J. Nicholas Francis, Joseph S Redman, Debra M Eckert, and Michael S. Kay. Bioconjugate Chemistry, 2012, 23 (6), pp 1252-1258, May 1, 2012. DOI: 10.1021/bc300076f.

Multivalent Benzamidine Molecules for Plasmin Inhibition: Effect of Valency and Linker Length. Tanmaye Nallan Chakravarthula, Dr. Ziqian Zeng, Prof. Nathan J. Alves. ChemMedChem, Volume 17, Issue 22, (2022), 09/16/2022, https://doi.org/10.1002/cmdc.202200364.

Description

Fmoc-N-amido-dPEG®8-NHS ester, product number QBD-10995 contains an Fmoc-protected amine on one end of a short (28 atoms), single molecular weight, discrete-chain-length polyethylene glycol (dPEG®) spacer and the N-hydroxysuccinimidyl (NHS) ester of a propionic acid group on the other end. This product is ready for the direct introduction of a water-soluble, amphiphilic spacer into a peptide chain without the need to activate the carboxylic acid moiety. The Fmoc protecting group on the N-terminus of the molecule cleaves easily with standard peptide chemistry.

Fmoc-N-amido-dPEG®8-NHS ester permits our customers to insert a short dPEG® spacer into a peptide chain using solid-phase or solution-phase chemistry. The dPEG® linker attaches at the N-terminal end of the peptide chain or on the free amine side chain of amino acids such as lysine. Additional peptide synthesis can be carried out to extend the peptide further, creating a peptide with a flexible, hydrophilic linker or spacer in the middle. Also, the dPEG® chain can provide spacing in a synthetic construct where steric hindrance is a problem. Amphiphilic, non-immunogenic dPEG® increases the hydrodynamic volume and improves the water solubility of the peptide while remaining soluble in organic solvents. The Fmoc protecting group is removed easily with a solution of piperidine in N,N-dimethylformamide (DMF).

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Design of a modular tetrameric scaffold for the synthesis of membrane-localized D-peptide inhibitors of HIV-1 entry. J. Nicholas Francis, Joseph S Redman, Debra M Eckert, and Michael S. Kay. Bioconjugate Chemistry, 2012, 23 (6), pp 1252-1258, May 1, 2012. DOI: 10.1021/bc300076f.

Novel Synthetic Route to Peptide-Capped Gold Nanoparticles, Takeshi Serizawa, Yu Hirai, and Mamoru Aizawa. Langmuir. 2009, 25 (20), pp 12229–12234. September 21, 2009. DOI: 10.1021/la9021799.

Multivalent Benzamidine Molecules for Plasmin Inhibition: Effect of Valency and Linker Length. Tanmaye Nallan Chakravarthula, Dr. Ziqian Zeng, Prof. Nathan J. Alves. ChemMedChem, Volume 17, Issue 22, (2022), 09/16/2022, https://doi.org/10.1002/cmdc.202200364.

Description

Fmoc-N-amido-dPEG®4-NHS ester, product number QBD-10994 contains an Fmoc-protected amine on one end of a short (16 atoms), single molecular weight, discrete-chain-length polyethylene glycol (dPEG®) spacer and the N-hydroxysuccinimidyl (NHS) ester of a propionic acid group on the other end. This product is ready for the direct introduction of a water-soluble, amphiphilic spacer into a peptide chain. The Fmoc protecting group on the N-terminus of the molecule cleaves easily with standard peptide chemistry.

Fmoc-N-amido-dPEG®4-NHS ester permits our customers to insert a short dPEG® spacer into a peptide chain using standard Fmoc chemistry without the need to activate the acid terminus for conjugation. The product works equally well in solid-phase and solution-phase synthetic processes. The dPEG® linker attaches at the N-terminal end of the peptide chain or on the free amine side chain of amino acids such as lysine. Additional peptide synthesis can be carried out to extend the peptide further, creating a peptide with a flexible, hydrophilic linker or spacer in the middle. Also, the dPEG® chain can provide spacing in a synthetic construct where steric hindrance is a problem. Amphiphilic, non-immunogenic dPEG® increases the hydrodynamic volume and improves the water solubility of the conjugate while remaining soluble in organic solvents. The Fmoc protecting group is removed easily with a solution of piperidine in N,N-dimethylformamide (DMF).

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Design of a modular tetrameric scaffold for the synthesis of membrane-localized D-peptide inhibitors of HIV-1 entry. J. Nicholas Francis, Joseph S Redman, Debra M Eckert, and Michael S. Kay. Bioconjugate Chemistry, 2012, 23 (6), pp 1252-1258, May 1, 2012. DOI: 10.1021/bc300076f.

Multivalent Benzamidine Molecules for Plasmin Inhibition: Effect of Valency and Linker Length. Tanmaye Nallan Chakravarthula, Dr. Ziqian Zeng, Prof. Nathan J. Alves. ChemMedChem, Volume 17, Issue 22, (2022), 09/16/2022, https://doi.org/10.1002/cmdc.202200364.

Description

Bis-dPEG®7-NHS ester, product number QBD-10988, is a homobifunctional, amine-reactive, single molecular weight PEG crosslinker with a short (25 atoms, 28.6 Å) discrete PEG (dPEG®) chain length. Each end of the chain terminates as the N-hydroxysuccinimidyl (NHS) ester of propionic acid. Unlike traditional hydrophobic crosslinkers, Bis-dPEG®7-NHS ester will not cause problems such as aggregation, precipitation, and inactivation when conjugated to biomolecules. As a homobifunctional, amine-reactive crosslinker, the primary uses for QBD-10988 are intermolecular conjugation of biomolecules with free, surface-accessible amines and intramolecular modification of biomolecules using free, surface-accessible amines. Because QBD-10988 is one in a line of similar products, Bis-dPEG®7-NHS ester can be used with other products in the same line to probe the effect of different linker lengths on the performance of crosslinked or intramolecularly modified biomolecules.

NHS esters react with free amines such as the ε-amines of lysine. The optimal pH range for NHS esters to react with free amines is 7.0 – 7.5. However, NHS esters can react with free amines with pH as low as 6.5. NHS esters are susceptible to hydrolysis in aqueous media. As the pH increases, the hydrolysis rate of the ester increases. Thus, we strongly discourage storing Bis-dPEG®7-NHS ester in water or aqueous buffer. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use. If customers desire to store the product in solution, we recommend the use of a pure, anhydrous, water-miscible solvent such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC), or N,N-dimethylformamide (DMF). DMSO, DMAC, or DMF can be dried chemically or by storing for a minimum of 24 hours over 3 Å molecular sieves. With DMF, use only fresh solvent as the compound decomposes over time to form free amines that will react with the NHS esters.

Specifications

Documents

References

Inhibition of HLA-DQ2 Mediated Antigen Presentation by Analogues of a High Affinity 33-Residue Peptide from α2-Gliadin. Jiang Xia, Matthew Siegel, Elin Bergseng, Ludvig M. Sollid, and Chaitan Khosla. Journal of the American Chemical Society 2006 128 (6) pp 1859-1867 February 15, 2006. DOI:10.1021/ja056423o.

Description

Bis-dPEG®17-NHS ester, product number QBD-10979, is a homobifunctional, amine-reactive, single molecular weight PEG crosslinker with a long (55 atoms, 64.4 Å) discrete PEG (dPEG®) chain length. Each end of the chain terminates as the N-hydroxysuccinimidyl (NHS) ester of propionic acid. Unlike traditional hydrophobic crosslinkers, Bis-dPEG®17-NHS ester will not cause problems such as aggregation, precipitation, and inactivation when conjugated to biomolecules. As a homobifunctional, amine-reactive crosslinker, the primary uses for QBD-10979 are intermolecular conjugation of biomolecules with free, surface-accessible amines and intramolecular modification of biomolecules using free, surface-accessible amines. Because QBD-10979 is one in a line of similar products, Bis-dPEG®17-NHS ester can be used with other products in the same line to probe the effect of different linker lengths on the performance of crosslinked or intramolecularly modified biomolecules.

NHS esters react with free amines such as the ε-amines of lysine. The optimal pH range for NHS esters to react with free amines is 7.0 – 7.5. However, NHS esters can react with free amines with pH as low as 6.5. NHS esters are susceptible to hydrolysis in aqueous media. As the pH increases, the hydrolysis rate of the ester increases. Thus, we strongly discourage storing Bis-dPEG®17-NHS ester in water or aqueous buffer. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use. If customers desire to store the product in solution, we recommend the use of a pure, anhydrous, water-miscible solvent such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC), or N,N-dimethylformamide (DMF). DMSO, DMAC, or DMF can be dried chemically or by storing for a minimum of 24 hours over 3 Å molecular sieves. With DMF, use only fresh solvent as the compound decomposes over time to form free amines that will react with the NHS esters.

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Redox-Responsive Self-Assembly of Amphiphilic Multiblock Rod–Coil Polymers. Taek-Gyoung Kim, Chingu Kim, and Ji-Woong Park. Macromolecules. 2017, 50 (20) pp 8185–8191. 10/4/2017. DOI: 10.1021/acs.macromol.7b01650.

Description

Bis-dPEG®25-NHS ester, product number QBD-10968, is a homobifunctional, amine-reactive, single molecular weight PEG crosslinker with a long (79 atoms, 93.0 Å) discrete PEG (dPEG®) chain length. Each end of the chain terminates as the N-hydroxysuccinimidyl (NHS) ester of propionic acid. Unlike traditional hydrophobic crosslinkers, Bis-dPEG®25-NHS ester will not cause problems such as aggregation, precipitation, and inactivation when conjugated to biomolecules. As a homobifunctional, amine-reactive crosslinker, the primary uses for QBD-10968 are intermolecular conjugation of biomolecules with free, surface-accessible amines and intramolecular modification of biomolecules using free, surface-accessible amines. Because QBD-10968 is one in a line of similar products, Bis-dPEG®25-NHS ester can be used with other products in the same line to probe the effect of different linker lengths on the performance of crosslinked or intramolecularly modified biomolecules.

NHS esters react with free amines such as the ε-amines of lysine. The optimal pH range for NHS esters to react with free amines is 7.0 – 7.5. However, NHS esters can react with free amines with pH as low as 6.5. NHS esters are susceptible to hydrolysis in aqueous media. As the pH increases, the hydrolysis rate of the ester increases. Thus, we strongly discourage storing Bis-dPEG®25-NHS ester in water or aqueous buffer. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use. If customers desire to store the product in solution, we recommend the use of a pure, anhydrous, water-miscible solvent such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC), or N,N-dimethylformamide (DMF). DMSO, DMAC, or DMF can be dried chemically or by storing for a minimum of 24 hours over 3 Å molecular sieves. With DMF, use only fresh solvent as the compound decomposes over time to form free amines that will react with the NHS esters.

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Multivalent Benzamidine Molecules for Plasmin Inhibition: Effect of Valency and Linker Length. Tanmaye Nallan Chakravarthula, Dr. Ziqian Zeng, Prof. Nathan J. Alves. ChemMedChem, Volume 17, Issue 22, (2022), 09/16/2022, https://doi.org/10.1002/cmdc.202200364.

Description

Bis-dPEG®21-NHS ester, product number QBD-10956, is a homobifunctional, amine-reactive, single molecular weight PEG crosslinker with a long (67 atoms, 79.1 Å) discrete PEG (dPEG®) chain length. Each end of the chain terminates as the N-hydroxysuccinimidyl (NHS) ester of propionic acid. Unlike traditional hydrophobic crosslinkers, Bis-dPEG®21-NHS ester will not cause problems such as aggregation, precipitation, and inactivation when conjugated to biomolecules. As a homobifunctional, amine-reactive crosslinker, the primary uses for QBD-10956 are intermolecular conjugation of biomolecules with free, surface-accessible amines and intramolecular modification of biomolecules using free, surface-accessible amines. Because QBD-10956 is one in a line of similar products, Bis-dPEG®21-NHS ester can be used with other products in the same line to probe the effect of different linker lengths on the performance of crosslinked or intramolecularly modified biomolecules.

NHS esters react with free amines such as the ε-amines of lysine. The optimal pH range for NHS esters to react with free amines is 7.0 – 7.5. However, NHS esters can react with free amines with pH as low as 6.5. NHS esters are susceptible to hydrolysis in aqueous media. As the pH increases, the hydrolysis rate of the ester increases. Thus, we strongly discourage storing Bis-dPEG®21-NHS ester in water or aqueous buffer. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use. If customers desire to store the product in solution, we recommend the use of a pure, anhydrous, water-miscible solvent such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC), or N,N-dimethylformamide (DMF). DMSO, DMAC, or DMF can be dried chemically or by storing for a minimum of 24 hours over 3 Å molecular sieves. With DMF, use only fresh solvent as the compound decomposes over time to form free amines that will react with the NHS esters.

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Redox-Responsive Self-Assembly of Amphiphilic Multiblock Rod–Coil Polymers. Taek-Gyoung Kim, Chingu Kim, and Ji-Woong Park. Macromolecules. 2017, 50 (20) pp 8185–8191. 10/4/2017. DOI: 10.1021/acs.macromol.7b01650.

Description

Bis-dPEG®13-NHS ester, product number QBD-10954, is a homobifunctional, amine-reactive, single molecular weight PEG crosslinker with a medium-length (43 atoms, 50.1 Å) discrete PEG (dPEG®) chain length. Each end of the chain terminates as the N-hydroxysuccinimidyl (NHS) ester of propionic acid. Unlike traditional hydrophobic crosslinkers, Bis-dPEG®13-NHS ester will not cause problems such as aggregation, precipitation, and inactivation when conjugated to biomolecules. As a homobifunctional, amine-reactive crosslinker, the primary uses for QBD-10954 are intermolecular conjugation of biomolecules with free, surface-accessible amines and intramolecular modification of biomolecules using free, surface-accessible amines. Because QBD-10954 is one in a line of similar products, Bis-dPEG®13-NHS ester can be used with other products in the same line to probe the effect of different linker lengths on the performance of crosslinked or intramolecularly modified biomolecules.

NHS esters react with free amines such as the ε-amines of lysine. The optimal pH range for NHS esters to react with free amines is 7.0 – 7.5. However, NHS esters can react with free amines with pH as low as 6.5. NHS esters are susceptible to hydrolysis in aqueous media. As the pH increases, the hydrolysis rate of the ester increases. Thus, we strongly discourage storing Bis-dPEG®13-NHS ester in water or aqueous buffer. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use. If customers desire to store the product in solution, we recommend the use of a pure, anhydrous, water-miscible solvent such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC), or N,N-dimethylformamide (DMF). DMSO, DMAC, or DMF can be dried chemically or by storing for a minimum of 24 hours over 3 Å molecular sieves. With DMF, use only fresh solvent as the compound decomposes over time to form free amines that will react with the NHS esters.

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.

Redox-Responsive Self-Assembly of Amphiphilic Multiblock Rod–Coil Polymers. Taek-Gyoung Kim, Chingu Kim, and Ji-Woong Park. Macromolecules. 2017, 50 (20) pp 8185–8191. 10/4/2017. DOI: 10.1021/acs.macromol.7b01650.

Multivalent Benzamidine Molecules for Plasmin Inhibition: Effect of Valency and Linker Length. Tanmaye Nallan Chakravarthula, Dr. Ziqian Zeng, Prof. Nathan J. Alves. ChemMedChem, Volume 17, Issue 22, (2022), 09/16/2022, https://doi.org/10.1002/cmdc.202200364.

Description

MAL-dPEG®36-NHS ester, product number QBD-10904, is a crosslinking reagent that joins a sulfhydryl to a free amine through a hydrophilic bridge. The sulfhydryl groups react with a maleimide group via a Michael addition reaction. The amines form amide bonds with the crosslinker by nucleophilic substitution of the N-hydroxysuccinimidyl (NHS) ester of a carboxylic acid group. The maleimide and NHS functional groups on the crosslinking compound sit at either end of a long (118 atoms, 134.8 Å), discrete-length polyethylene glycol (dPEG®) chain.

Reactions that join free amines with free thiols are among the most popular, most useful crosslinking reactions in bioconjugate chemistry. These reactions require heterobifunctional reagents that bridge the two groups. Traditional crosslinkers are hydrophobic molecules. Vector Laboratories’ dPEG® crosslinking products are water-soluble, amphiphilic, single molecular weight PEG compounds with discrete chain lengths.

The conjugation of conventional hydrophobic crosslinking reagents to biomolecules almost inevitably triggers problems such as aggregation and precipitation of the conjugates. These problems do not occur with our water-soluble, non-immunogenic dPEG® crosslinkers.

Because NHS esters hydrolyze readily in water or aqueous buffer, the NHS ester end of the molecule must conjugate to a target molecule before conjugating the maleimide end of the molecule. At pH 7.0 – 7.5, NHS esters react optimally with free amines. However, NHS esters can react with free amines with pH as low as 6.5. As the pH increases, the hydrolysis rate of the NHS ester increases. Indeed, at pH 8 and 25°C, the half-life of an NHS ester in aqueous media is one hour, while at pH 8.6 and 4°C, the half-life falls to ten (10) minutes.[3] Thus, we strongly discourage storing MAL-dPEG®36-NHS ester, product number QBD-10904, in water or aqueous buffer. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use.

The reaction of the maleimide end of MAL-dPEG®36-NHS ester with a sulfhydryl proceeds optimally at pH 6.5 – 7.5. Use the lowest reasonable pH within this range. Above pH 7.5, free amines compete with free thiols at the maleimide reaction site, which can cause confusing results. Moreover, at higher pH values, the maleimide ring may open to form unreactive maleamic acid.

The use of MAL-dPEG®36-NHS ester, product number QBD-10904, has been published in numerous scientific paper and patents. The following list highlights some of the more interesting uses of this product:
development of extracellular drug conjugates (EDCs), a type of ADC for extracellular markers;
targeted delivery of cancer drugs;
as a long, flexible tether for atomic force microscopy (AFM); and
as a surface coating for amine-functionalized nanoparticle surfaces.

Specifications

Documents

References

Greg T. Hermanson, Bioconjugate Techniques, 2nd Edition, Elsevier Inc., Burlington, MA 01803, April, 2008 (ISBN-13: 978-0-12-370501-3; ISBN-10: 0-12-370501-0); See pp. 276-335 for general description and use of heterobifunctional crosslinkers, as well as his specific discussion with protocols of our MAL-dPEG®x-NHS esters on pp. 718-722.

Greg T. Hermanson, Bioconjugate Techniques, 3rd Edition, Elsevier, Waltham, MA 02451, 2013, ISBN 978-0-12-382239-0; See Chapter 18, Discrete PEG Reagents, pp. 787-821, for a full overview of the dPEG® products.