Description

NH2-dPEG®4-Glu(OH)-[NH-dPEG®4-Glu(OH)]2-NH-m-dPEG®24, product number QBD-11644, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The free primary amine of NH2-dPEG®4-Glu(OH)-[NH-dPEG®4-Glu(OH)]2-NH-m-dPEG®24, QBD-11644 reacts with carboxylic acids and their active esters (TFP esters, NHS esters) to form stable amide bonds. It is the attachment point for the Sidewinder™ to the biomolecule (e.g., mAb, Fab, Fab’, targeting peptide, and so forth). The backbone contains three (3) carboxylic acid sidearms that react with free amines. Following reaction, protection, or functionalization of the attachment point amino group, the carboxylic acid sidearms can be conjugated to an amine-containing payload. The conjugation can be done directly using EDC or another suitable carbodimide. Alternatively, the carboxylic acids can be functionalized with N-hydroxysuccinimide (NHS) or 2,3,5,6-tetrafluorophenol (TFP) to form the active esters, which can then be reacted with a free amine-containing payload.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. NH2-dPEG®4-Glu(OH)-[NH-dPEG®4-Glu(OH)]2-NH-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the amine attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

NH2-dPEG®4-Glu(OH)-NH-m-dPEG®24, product number QBD-11643, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The free primary amine of NH2-dPEG®4-Glu(OH)-NH-m-dPEG®24, QBD-11643, reacts with carboxylic acids and their active esters (TFP esters, NHS esters) to form stable amide bonds. It is the attachment point for the Sidewinder™ to the biomolecule (e.g., mAb, Fab, Fab’, targeting peptide, and so forth). The backbone contains one carboxylic acid sidearm that reacts with free amines. Following reaction, protection, or functionalization of the attachment point amino group, the carboxylic acid sidearm can be conjugated to an amine-containing payload. The conjugation can be done directly using EDC or another suitable carbodimide. Alternatively, the carboxylic acid can be functionalized with N-hydroxysuccinimide (NHS) or 2,3,5,6-tetrafluorophenol (TFP) to form the active ester, which can then be reacted with a free amine-containing payload.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. NH2-dPEG®4-Glu(OH)-NH-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the amine attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

Bis-MAL-Lysine-dPEG®4-dPEG®12-Tris(m-dPEG®24)3, product number QBD-11633, is a unique product from Vector Laboratories. It consists of a carboxylic-acid terminated, branched dPEG® construct built around a tris core and functionalized with a short dPEG® linker that contains two thiol-reactive maleimide groups attached to lysine. The dPEG® spacers are 152 and 156 atoms, with average lengths of 113.0 and 115.4 Å. Three uncharged methoxy-terminated dPEG® spacers branch from the tris core of this product. Bis-MAL-Lysine-dPEG®4-dPEG®12-Tris(m-dPEG®24)3 is designed to modify the pharmacodynamics (PD), pharmacokinetics (PK), and biodistribution (BD) of conjugated biomolecules, while the bis-maleimide moiety is designed to bridge disulfide bonds by forming stable thioether bonds through the thiol-maleimide reaction.

This product is designed for modifying biomolecules like antibodies and antibody fragments but can be used in any bioconjugate application where free thiols are available for reaction. The two maleimide groups can bridge a reduced disulfide bond through the thiol-maleimide reaction, forming stable thioether bonds. Potential product applications include reducing or eradicating renal clearance, extending in vivo circulating half-life, and suppressing immune responses to conjugates.

Vector Laboratories’ dPEG® technology provides high-quality, single molecular weight, discrete chain-length PEG (dPEG®) products for bioconjugation in therapeutic, diagnostic, and clinical research applications. Unlike traditional, non-uniform polymer PEGs, dPEG® products are synthesized in stepwise fashion from high-purity starting materials. The amphiphilic dPEG® construct imparts hydrophilicity to conjugates, reduces or eliminates the conjugates’ antigenicity, and increases the hydrodynamic volume of conjugated molecules. With increased hydrodynamic volume, the renal clearance of conjugate molecules is reduced or eliminated. Moreover, optimization of the conjugate molecule’s BD, PK, and PD is possible.

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

Bis-MAL-Lysine-dPEG®4-dPEG®12-Tris(-dPEG®24 acid)3, product number QBD-11630, is a unique product from Vector Laboratories. It consists of a carboxylic-acid terminated, branched dPEG® construct built around a tris core and functionalized with a short dPEG® linker that contains two thiol-reactive maleimide groups attached to lysine. The dPEG® spacers are 152 and 156 atoms, with average lengths of 113.0 and 115.4 Å. The tris-core branched portion of this product is designed to modify the pharmacodynamics (PD), pharmacokinetics (PK), and biodistribution (BD) of conjugated biomolecules, while the bis-maleimide moiety is designed to bridge disulfide bonds by forming stable thioether bonds through the thiol-maleimide reaction.

This product is designed for modifying biomolecules like antibodies and antibody fragments but can be used in any bioconjugate application where free thiols are available for reaction. The two maleimide groups can bridge a reduced disulfide bond through the thiol-maleimide reaction, forming stable thioether bonds. Potential product applications include reducing or eradicating renal clearance, extending in vivo circulating half-life, and suppressing immune responses to conjugates. Users should note that the free carboxylates on the three long arms of the molecule may alter the charge of conjugates formed with Bis-MAL-Lysine-dPEG®4-dPEG®12-Tris(-dPEG®24 acid)3.

Vector Laboratories’ dPEG® technology provides high-quality, single molecular weight, discrete chain-length PEG (dPEG®) products for bioconjugation in therapeutic, diagnostic, and clinical research applications. Unlike traditional, non-uniform polymer PEGs, dPEG® products are synthesized in stepwise fashion from high-purity starting materials. The amphiphilic dPEG® construct imparts hydrophilicity to conjugates, reduces or eliminates the conjugates’ antigenicity, and increases the hydrodynamic volume of conjugated molecules. With increased hydrodynamic volume, the renal clearance of conjugate molecules is reduced or eliminated. Moreover, optimization of the conjugate molecule’s BD, PK, and PD is possible.

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

MAL-dPEG®4-Glu(TFP)-NH-dPEG®4-Glu(TFP)-m-dPEG®24, product number QBD-11626, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The maleimide group of MAL-dPEG®4-Glu(TFP)-NH-dPEG®4-Glu(TFP)-m-dPEG®24, product number QBD-11626, reacts with free thiols to form stable thioether bonds. It is the attachment point for the Sidewinder™ to the biomolecule (e.g., mAb, Fab, Fab’, targeting peptide, and so forth). The backbone contains two carboxylic acid sidearms functionalized as 2,3,5,6-tetrafluorophenyl (TFP) esters. The TFP esters react with free amines in an optimal pH range of 7.5 – 8.0 and are more reactive toward amines than NHS esters within the optimal pH range.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. MAL-dPEG®4-Glu(TFP)-NH-dPEG®4-Glu(TFP)-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the maleimide attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

NH2-dPEG®4-Glu(OH)-NH-dPEG®4-Glu(OH)-m-dPEG®24, product number QBD-11624, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The free primary amine of NH2-dPEG®4-Glu(OH)-NH-dPEG®4-Glu(OH)-m-dPEG®24, product number QBD-11624, reacts with carboxylic acids or their active esters (NHS ester, TFP ester) to form stable amide bonds. It is the attachment point for the Sidewinder™ to the biomolecule (e.g., mAb, Fab, Fab’, targeting peptide, and so forth). The amine can be modified with a reactive group or conjugated directly to the carrier molecule. The backbone contains two carboxylic acid sidearms. After the primary amine is reacted, functionalized, or protected, the two sidearms can be conjugated to amine-containing payloads. The conjugation can be direct, using EDC or another suitable carbodiimide, or indirect, after first functionalizing the acid groups with N-hydroxysuccinimide (NHS ester) or 2,3,5,6-tetrafluorophenol (TFP ester) and then reacting the active esters with the amine-containing payloads.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. NH2-dPEG®4-Glu(OH)-NH-dPEG®4-Glu(OH)-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the amine attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

NH2-dPEG®4-Lys(t-boc)-NH-m-dPEG®24, product number QBD-11598, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The free primary amine of NH2-dPEG®4-Lys(t-boc)-NH-m-dPEG®24, product number QBD-11598, reacts with carboxylic acids or their active esters (NHS ester, TFP ester) to form stable amide bonds. The sidearm is functionalized as a boc-protected amine. It can be deprotected easily with trifluoroacetic or formic acid, exposing the amine for reaction with a payload containing a suitable reactive group.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. NH2-dPEG®4-Lys(t-boc)-NH-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the amine attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

MAL-dPEG®4-Glu(TFP)-NH-m-dPEG®24, product number QBD-11581, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The maleimide reactive group of MAL-dPEG®4-Glu(TFP)-NH-m-dPEG®24, product number QBD-11581, reacts with free thiols on the biomolecule through the thiol-maleimide reaction (a Michael addition reaction) to form a stable thioether bond. The sidearm is functionalized as the 2,3,5,6-tetrafluorophenyl ester (TFP ester) and reacts with free amines to form stable amide bonds. TFP esters have an optimal reaction pH range of 7.5 – 8.0. They are more hydrolytically stable than NHS esters and more reactive toward amines than NHS esters in the optimal pH range.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. MAL-dPEG®4-Glu(TFP)-NH-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the maleimide attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

MAL-dPEG®4-Glu(OH)-NH-m-dPEG®24, product number QBD-11580, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The maleimide reactive group of MAL-dPEG®4-Glu(OH)-NH-m-dPEG®24, product number QBD-11580, reacts with free thiols on the biomolecule through the thiol-maleimide reaction (a Michael addition reaction) to form a stable thioether bond. The sidearm is an amine-reactive carboxylic acid. It can be reacted directly with free amines to form stable amide bonds using a carbodiimide like EDC. Alternatively, the carboxylic acid can be functionalized as the active ester with N-hydroxysuccinimide (NHS ester) or 2,3,5,6-tetrafluorophenol (TFP ester) and then reacted with free amines.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload (e.g., a cytotoxin) close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have a dispersed range of PEG chain lengths, each with a unique molecular weight. Unlike dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. MAL-dPEG®4-Glu(OH)-NH-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with other reactivities, change the maleimide attachment group to another reactive group, and many more customizations. Please inquire about your specific needs.

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

MAL-dPEG®4-Lys(5(6)-carboxyfluorescein)-NH-m-dPEG®24, product number QBD-11577, is one of Vector Laboratories’ unique, patented class of modular, designable payload delivery reagents called Sidewinder™. Sidewinder™ products are built on a discrete PEG (dPEG®) backbone for use in antibody-drug conjugates (ADCs) and related constructs. The payload (cytotoxin, dye, small molecule) loads onto the chain’s sidearm. The distal end’s methoxy-terminated dPEG®24 spacer protects payloads and modifies performance.

The maleimide reactive group of MAL-dPEG®4-Lys(5(6)-carboxyfluorescein)-NH-m-dPEG®24, product number QBD-11577 reacts with free thiols on the biomolecule through the thiol-maleimide reaction (a Michael addition reaction). The sidearm is functionalized with 5(6)-carboxyfluorescein (ex/em = 493/517) and can be used to track cell trafficking and internalization of a conjugated molecule such as an antibody or antibody fragment.

Sidewinder™ products are designed to facilitate the creation of stable, high-DAR ADCs. Published research has shown that putting a hydrophobic payload (e.g., a cytotoxin) close to the antibody surface and protecting it with a SuperHydrophilic™ dPEG® construct is better by many measures of efficacy than putting the payload at the distal end of the linker. This molecule can also be used to modify and optimize BD, cell trafficking and internalization, serum half-life, and immunogenicity.

The dPEG® linkers and spacers in the Sidewinder™ construct are uniform, single molecular-weight PEGs with discrete chain lengths. This differs from traditional, non-uniform polymer PEG linkers and spacers, which have a dispersed range of PEG chain lengths, each with a unique molecular weight. In contrast to dispersed polymer PEGs, dPEG® products are high-purity compounds with reproducible purity profiles.

Sidewinder™ molecules are also fully designable. MAL-dPEG®4-Lys(5(6)-carboxyfluorescein)-NH-m-dPEG®24 can be modified to change the spacer lengths, add more sidearm attachment points, add different sidearm attachment points to carry payloads with different reactivities, change the maleimide attachment group to a different reactive group, and many more customizations. Please inquire about your specific needs.

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.