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®24-Tris(-dPEG®24-Tris (m-dPEG®24)3)3, product number QBD-11487, is a nine-branched, 15.4 kDa, sulfhydryl-reactive, monodispersed PEGylation reagent built around tris cores from high-purity, single molecular weight, discrete PEG (dPEG®) compounds. The attachment point is a thiol-reactive maleimide group. Nine uncharged methoxy-terminated dPEG®24 linkers arising from four tris cores in a 1:3 arrangement form the branches. The average dPEG® spacer length from the maleimide ring attachment point to the terminal methoxy groups is 247 atoms (158.8 Å). This product is designed for biomolecular conjugation to modulate the pharmacokinetics (PK) and biodistribution (BD) of biomolecules such as antibodies or other proteins. It may also be used to passivate surfaces to prevent non-specific interactions.

Vector Laboratories’ dPEG® technology uses high-purity, single molecular-weight PEG linkers and spacers with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have an intractable mixture of different chain lengths of PEG, where each length of PEG in the mix has a unique molecular weight. Analyzing dPEG® products and conjugates made with them is far more straightforward than analyzing non-uniform PEG products and their conjugates.

The terminal maleimide group in MAL-dPEG®24-Tris(-dPEG®24-Tris(m-dPEG®24)3)3, product number QBD-11487, provides the sole attachment point for the dPEG® construct to join a free thiol (sulfhydryl) group, forming a stable thioether bond. Surface-accessible, free thiols are uncommon in biomolecules but may be preferred over surface-accessible amines for PEGylation of biomolecules. Free thiols can also be exposed by creating antibody fragments or reduction reactions targeting disulfide bonds.

PEGylation of biomolecules with MAL-dPEG®24-Tris(-dPEG®24-Tris(m-dPEG®24)3)3 greatly increases a conjugate molecule’s hydrodynamic volume and water solubility and shields the conjugate from opsonization by the immune system. These effects prevent renal clearance of the conjugate by the body and reduce or eliminate opsonization, extending the conjugate’s serum half-life. The longer serum half-life can lead to lower dosing requirements for the PEGylated conjugate compared to the non-PEGylated conjugate while maintaining diagnostic or therapeutic efficacy.

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

Amino-dPEG®24-Tris(-dPEG®24-Tris(m-dPEG®24)3)3, product number QBD-11486, is a nine-branched, 15.4 kDa, PEGylation reagent built around tris cores from high-purity, single molecular weight, discrete PEG (dPEG®) compounds. The attachment point is a carboxylate-reactive primary amine. Nine uncharged methoxy-terminated dPEG®24 linkers form the branches. The nine branch points arise from four tris cores in a 1:3 arrangement. The average dPEG® spacer length from the primary amine attachment point to the terminal methoxy groups is 241 atoms (155.1 Å). This product is designed for biomolecular conjugation to modulate the pharmacokinetics (PK) and biodistribution (BD) of biomolecules such as antibodies or other proteins. It may also be used to passivate surfaces to prevent non-specific interactions.

PEGylation of biomolecules with Amino-dPEG®24-Tris(-dPEG®24-Tris(m-dPEG®24)3)3 greatly increases a conjugate molecule’s hydrodynamic volume and water solubility and shields the conjugate from opsonization by the immune system. These effects prevent renal clearance of the conjugate by the body and reduce or eliminate opsonization, extending the conjugate’s serum half-life. The longer serum half-life can lead to lower dosing requirements for the PEGylated conjugate compared to the non-PEGylated conjugate while maintaining diagnostic or therapeutic efficacy.

Vector Laboratories’ dPEG® technology uses high-purity, single molecular-weight PEG linkers and spacers with discrete chain lengths. In contrast, traditional, non-uniform polymer PEG linkers and spacers have an intractable mixture of different chain lengths of PEG, where each length of PEG in the mix has a unique molecular weight. Analyzing dPEG® products and conjugates made with them is far more straightforward than analyzing non-uniform PEG products and their conjugates.

The free primary amine in Amino-dPEG®24-Tris(-dPEG®24-Tris(m-dPEG®24)3)3, product number QBD-11486, provides the sole attachment point for the dPEG® construct to connect with a carboxylate or the active ester (NHS ester, TFP ester) of a carboxylic acid, forming a stable amide bond. The carboxylate or active ester can be on a biomolecule (protein, protein fragment, or peptide) or surface (for example, nanoparticles functionalized with carboxylic acids or their active esters). The amine also reacts with aldehydes, which can be generated on the carbohydrate coats of glycoproteins. The amine and aldehyde reaction forms a labile Schiff base, which readily reduces under mild conditions to create a stable secondary amine. When using Amino-dPEG®24-Tris(-dPEG®24-Tris(m-dPEG®24)3)3 to modify charged biomolecules, users should be aware that the uncharged methyl groups likely will alter the overall charge of the conjugate.

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

Amino-dPEG®12-Tris(m-dPEG®24)3, product number QBD-11474, is a carboxylate-reactive, methyl-terminated, four-arm monodispersed PEG product designed to modulate the pharmacokinetics (PK) and biodistribution (BD) of conjugates. It can also be used in surface passivation of organic, inorganic, and biomolecular surfaces. Tris forms the core of the molecule. Three equal-length (76 atoms) methyl-terminated long arms plus one shorter (40 atoms) maleimido-terminated arm extend from the tris core. The total length of the product from the reactive amine to each of the terminal methyl groups is 121 atoms (99.8 Å).

The terminal primary amine reacts with carboxylic acids (carboxylates) and their active esters (e.g., NHS esters, TFP esters) to form stable amide bonds. The terminal amine also reacts with aldehydes to form a labile Schiff base that can be reduced to a stable secondary amine under mild conditions. The uncharged terminal methyl groups may alter the overall charge of the conjugate molecule.

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.

This product is designed for modifying biomolecules like antibodies and antibody fragments but can be used in any bioconjugate application where free carboxylates or their active esters are available for reaction. Potential product applications include reducing or eradicating renal clearance, extending in vivo circulating half-life, and suppressing immune responses to conjugates. Amino-dPEG®12-Tris(m-dPEG®24)3, product number QBD-11474, can passivate organic, inorganic, or biomoecular surfces to prevent non-specific, hydrophobic interactions.

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.

T114 Regulates Formation of the B-TFIID Complex and Is Critical for Metabolic Gene Regulation. Stéphan Hardivillé, Partha S. Banerjee, Ebru S. Selen Alpergin, Danielle M. Smith, Guanghui Han, JunfengMa, C. Conover Talbot Jr.,Ping Hu, Michael J.Wolfgang, Gerald W. Hart. Molecular Cell, 2019, 77. December 19, 2019. DOI 10.1016/j.molcel.2019.11.022

Description

MAL-dPEG®12-Tris(m-dPEG®24)3, product number QBD-11471, is a thiol-reactive, methyl-terminated, four-arm monodispersed PEG product designed to modulate biodistribution of conjugates. Tris forms the core of the molecule. Three equal-length methyl-terminated long arms plus one maleimido-terminated short arm extend from the tris core.

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.

The maleimidopropyl (MAL) group reacts chemoselectively with free thiols at pH 6.5 – 7.5 to form stable thioether bonds. Maleimide-thiol conjugations are click chemistry-like reactions and one of the most popular ways to form thioether bonds in biomolecules.

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. Potential product applications include reducing or eradicating renal clearance, extending in vivo circulating half-life, and suppressing immune responses to conjugates.

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.

Site specific discrete PEGylation of 124I-labeled mCC49 Fab’ fragments improves tumor microPET/CT imaging in mice. Haiming Ding, Michelle M. Carleton, Stephen P. Povoski, Keisha Milum, Krishan Kumar, Kothandaraman Shankaran, George H. Hinkle, David Colcher, Rich Brody, Paul D. Davis, Alex Pokora, Mitchell Phelps, Edward W. Martin Jr., and Michael F. Tweedle. Bioconjugate Chemistry. 2013, 24 (11) pp 1945-1954. October 4, 2013. DOI: 10.1021/bc400375f.

Tumor uptake of pegylated diabodies: Balancing systemic clearance and vascular transport. Qing Li, Jason B. White, Norman C. Peterson, Keith W. Rickert, Christopher O. Lloyd, Kevin L. Allen, Kim Rosenthal, Xizhe Gao, Herren Wu, William F. Dall’Acqua, M. Jack Borrok, and Ping Tsui. Journal of Controlled Release. 2018, 279 pp 126-135. April 6, 2018. DOI: 10.1016/j.jconrel.2018.04.013.

Description

MAL-dPEG®12-Tris(-dPEG®24-acid)3, product number QBD-11451, is a thiol- and amine-reactive, four-arm, monodispersed PEG with one arm shorter than the other three. MAL-dPEG®12-Tris(-dPEG®24-acid)3 is a monodispersed branched PEG compound built around a tris core. From the maleimide olefin to carbonyl carbon immediately before the tris core is 46 atoms. From the tris core to the carbonyl carbon on each branch is 83 atoms. The total linker length is 129 atoms. The maleimido group that terminates the short arm of this product reacts with sulfhydryl groups to form thioether bonds. It conjugates directly to target biomolecules.

This product is useful for charge modulation and elimination of renal clearance in drug delivery and imaging applications, among others. The dPEG® spacer length is from the maleimide olefin to the carbonyl carbon on each of the three long arms. The terminal carboxylic acid groups can be modified with various functional or reactive groups (e.g., NHS, TFP esters) or used as-is for charge modulation. In a peer-reviewed scientific publication, this product was shown to alter the biodistribution of the conjugate when used as a charge modulator on the antibody CC49, leading to improved microPET/CT imaging in mice.

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.

Site specific discrete PEGylation of 124I-labeled mCC49 Fab’ fragments improves tumor microPET/CT imaging in mice. Haiming Ding, Michelle M Carleton, Stephen P Povoski, Keisha Milum, Krishan Kumar, Kothandaraman Shankaran, George H Hinkle, David Colcher, Rich Brody, Paul D Davis, Alexander Pokora, Mitchell Phelps, Edward W. Martin, and Michael F. Tweedle. Bioconjugate Chemistry. 2013, October 4, 2013. DOI: 10.1021/bc400375f.

Description

Amino-dPEG®12-Tris(dPEG®24-t-butyl ester)3, product number QBD-11449, is a branched, four-arm, single molecular weight, discrete-length polyethylene glycol (dPEG®) product. Built around a tris core, the product consists of a carboxylate-reactive, medium-length (40 atoms) amino-dPEG®12 tail joined to one side of the tris core and three, equally long (76 atoms) tert-butyl-ester-protected dPEG®24 branches. The total length from the terminal, carboxylate-reactive amine tail to the carbonyl carbons on the branches is 126 atoms (102.8 Å, average).

Amino-dPEG®12-Tris(dPEG®24-t-butyl ester)3 increases the hydrodynamic volume and water solubility of conjugates made with it. The increased hydrodynamic volume protects conjugates from renal clearance and can shield them from the immune system.

The tert-butyl-ester-protected dPEG®24 branches can be deprotected with trifluoroacetic or formic acid. Once deprotected, the free carboxylic acids can be used for charge modification of the conjugate molecule or further functionalized for additional reactions. In addition to conjugate charge modification, potential uses for this product include PK/BD optimization of biomolecules, surface coating and passivation to prevent non-specific interactions, dendrimer construction, and payload delivery (cytotoxins, targeting molecules, etc.).

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

TFP-dPEG®4-(m-dPEG®11)3 ester, product number QBD-11401, is a water-soluble, amine-reactive, discrete PEG (dPEG®) PEGylation reagent built. This product is built around a tris core and consists of a short (21 atoms) amine-reactive 2,3,5,6-tetrafluorophenyl (TFP) ester “”tail”” on a uniform (i.e., monodispersed) PEG4 tail and three (3) medium-length (35 atoms) branches composed from methyl-terminated dPEG®11 (m-dPEG®11). The total dPEG® spacer length from the reactive end to the methyl termini is 63 atoms (74.1 Å average). TFP-dPEG®4-(m-dPEG®11)3 ester is used to PEGylate and modify amine-reactive biomolecules and surfaces. This hydrophilic branched dPEG® product greatly increases the conjugates’ hydrodynamic volumes, reducing immunogenicity and renal clearance. Moreover, this product reduces or eliminates non-specific binding to conjugates and surfaces.

TFP esters react with free amines like NHS esters to form stable amide bonds. TFP esters’ optimal reaction pH is 7.5 – 8.0, which is higher than NHS esters (optimal pH range 7.0 – 7.5). However, published research has shown that, within the optimal reaction pH range, TFP esters are more reactive toward amines than NHS esters are within their optimal pH range. Applications for TFP-dPEG®4-(m-dPEG®11)3 ester, product number QBD-11401, include the following:
conjugating proteins and other biomolecules to modify PK and BD;
PEGylating amine-coated surfaces (e.g., nanoparticles) to sterically shield the surfaces and reduce non-specific, hydrophobic interactions;
PEGylating amine-coated organic or inorganic surfaces (e.g., carbon, gold, silver nanoparticles) to reduce or eliminate immunogenicity;
PEGylating biomolecules to reduce renal clearance and increase serum half-life; and
PEGylating biomolecules to reduce immunogenicity and increase water solubility.

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.

Synthesis and Preliminary Biological Evaluation of High-Drug-Load Paclitaxel-Antibody Conjugates for Tumor-Targeted Chemotherapy, Sherly Quiles, Kevin P. Raisch, Leisa L. Sanford, James A. Bonner, and Ahmad Safavy, J Med. Chem., 2010, 53 (2), pp 586-594, December 3, 2009. DOI: 10.1021/jm900899g.

Visualizing Systemic Clearance and Cellular Level Biodistribution of Gold Nanorods by Intrinsic Two-Photon Luminescence, Ling Tong, Wei He, Yanshu Zhang, Wei Zheng, and Ji-Xin Cheng, Langmuir 2009, 25 (21), pp 12454-12459. DOI: 10.1021/la902992w.

A New Polyethyleneglycol-Derivatized Hemoglobin Derivative with Decreased Oxygen Affinity and Limited Toxicity. Oana Zolog, Augustin Mot, Florina Deac, Alina Roman, Eva Fischer-Fodor, Radu Silaghi-Dumitrescu. The Protein Journal. 2010 1 (30), pp 27-31. December 16, 2012 DOI: 10.1007/s10930-010-9298-5.

Improved pharmacokinetics and immunogenicity profile of organophosphorus hydrolase by chemical modification with polyethylene glycol. Boris N. Novikov, Janet K. Grimsley, Rory J. Kern, James R. Wild, Melinda E. Wales. Elsevier. 2010 146 (3) Pages 318-325 September 15, 2010. DOI: 10.1016/j.jconrel.2010.06.003.

Description

MAL-dPEG®4-(m-dPEG®24)3, product number QBD-10456, is a sulfhydryl-reactive, branched polyethylene glycol (PEG) product built around a tris core that is useful for modifying surfaces and biomolecules containing free thiols. Vector Laboratories, Inc. manufactures this monodispersed PEG product with a single molecular weight and discrete chain length and sells it under the dPEG® tradename. MAL-dPEG®4-(m-dPEG®24)3 increases the hydrophilicity of conjugated molecules; reduces non-specific, hydrophobic interactions; and decreases or eliminates the antigenicity of conjugates. Also, because it is a single molecule, the analysis of conjugates made with MAL-dPEG®4-(m-dPEG®24)3 is simplified compared to the analysis of conjugates prepared with traditional dispersed PEG products.

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). Chapter 1, p. 30.

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.