Description

DBCO-dPEG®24-TFP ester, product number QBD-11370, is a heterobifunctional, bioorthogonal crosslinker designed to join azides and amines across a long (76 atoms, 88.8 Å), flexible, hydrophilic, single molecular weight, discrete PEG (dPEG®) spacer. The tetrafluorophenyl (TFP) ester reacts specifically with free amines to form amide bonds; the optimum reaction pH is 7.5 – 8.0. The dibenzylcyclooctyne (DBCO) moiety selectively forms triazole linkages with azides via a click chemistry reaction known as strain-promoted azide-alkyne cycloaddition (SPAAC), also known as copper-free click chemistry. The amphiphilic dPEG® linker increases conjugates’ hydrodynamic volumes, and it can be used to create space in sterically crowded supramolecular constructs.

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). Specifically see pp. 726-729 in his Chapter 18 on discrete PEG compounds for pegylation applications.

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

Hydroxy-dPEG®24-TFP ester, product number QBD-11349, is a long (76 atoms, 88.8 Å), hydroxy-terminated, single molecular weight, discrete polyethylene glycol (dPEG®) compound functionalized with a 2,3,5,6-tetrafluorophenyl (TFP) ester for conjugation to primary and secondary amines. This product can be used for modification of amine-functionalized surfaces (e.g., silica, glass), modification of proteins and peptides at accessible amine sites on the molecules, the construction of discrete PEG dendrimers, and many other applications. The free hydroxy end of the dPEG® spacer can be functionalized for further reactions or left unmodified to increase hydrophilicity or modify the charge of conjugate molecules and 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). Specifically see pp. 726-729 in his Chapter 18 on discrete PEG compounds for pegylation applications.

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

Bromoacetamido-dPEG®24-amido-DBCO, product number QBD-11224, combines a thiol-reactive bromoacetyl group with dibenzylcyclooctyne (DBCO, also known as DIBAC), a copper-free click chemistry reactive group. The two reactive groups link via a long (76 atoms, 90.0 Å), flexible, single molecular weight, discrete polyethylene glycol (dPEG®) linker. The bromoacetyl group reacts chemoselectively with thiols at pH ≥ 8.0. This differs from the maleimide group, which reacts chemoselectively with sulfhydryls within the range of pH 6.5 – 7.5. The DBCO moiety is a strained cyclooctyne ring flanked by two benzyl rings on either side. DBCO was designed for strain promoted azide-alkyne cycloaddition (SPAAC), also known as copper-free click chemistry.

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). Specifically see pp. 726-729 in his Chapter 18 on discrete PEG compounds for pegylation applications.

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

Bromoacetamido-dPEG®24-TFP ester, product number QBD-11203, is a long (78 atoms, 91.2 Å), single molecular weight, discrete PEG (dPEG®) crosslinker functionalized with a thiol-reactive bromoacetate group on one end and an amine-reactive 2,3,5,6-tetrafluorophenyl (TFP) ester on the other.

The long, flexible, non-immunogenic dPEG® crosslinker increases the hydrodynamic volumes of conjugates in aqueous media, thereby increasing water solubility. The increased hydrodynamic volume can reduce or eliminate conjugate molecules’ renal clearance and shield conjugates from opsonization.

The bromoacetate moiety is an alternative to the maleimide group, reacting chemoselectively with free thiols at pH ≥8.0. It is useful for situations where the conjugate molecule needs to be kept at a high pH, above the range where maleimides can be used effectively, or in constructs where maleimide groups are unstable.

TFP esters are an alternate reactive group to the N-hydroxysuccinimidyl (NHS) ester and reacts with amines at an optimal pH range of 7.5 – 8.0, higher than the optimal range for NHS esters (pH 7.0 – 7.5). TFP esters are more hydrolytically stable than NHS esters, and they are more reactive toward amines in their optimal pH range than NHS esters are within the pH range 7.0 – 7.5.

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®24-TFP ester, product number QBD-11007 contains an Fmoc-protected amine on one end of a long (76 atoms), single molecular weight, discrete-chain-length polyethylene glycol (dPEG®) spacer and the tetrafluorophenyl (TFP) 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®24-TFP ester permits our customers to insert a 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. In aqueous solutions, TFP esters are more hydrolytically stable than NHS esters and have an optimum pH range of 7.5 – 8.0 for conjugation. 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 or joining two different peptides across the dPEG® bridge. In addition, 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.

Description

Amino-dPEG®24-OH, product number QBD-10868, also known as Amino-dPEG®24-alcohol, is a long (71 atoms, 86.0 Å), monodispersed PEGylation reagent designed to modify surfaces and biomolecules. One end of the molecule terminates with a primary amine, while the other end terminates with a primary alcohol group. This extremely hydrophilic PEGylation reagent reacts with carboxylate groups via the primary amine, leaving the hydroxy terminus free for functionalization and further reactions or as a hydrophilicity or charge modifier for the conjugate molecule.

The most common uses for Amino-dPEG®24-OH include modifying biomolecules and passivating surfaces with a highly hydrophilic coating. The primary amine on one end of the dPEG® linker reacts with carboxylates to form stable amide bonds and with aldehydes and ketones to form labile Schiff bases that can be reduced to secondary amines under mild conditions for greater stability. Conjugations with this molecule most commonly use the amine-carboxylate reaction with a carbodiimide such as EDC. Alternatively, activation of carboxylate as the NHS or TFP ester followed by reaction under slightly basic conditions also permits conjugation of the carboxylate and amino moieties.

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.

Real-Time Video Imaging of Protease Expression In Vivo. Lei Zhu, Jin Xie, Magdalena Swierczewska, Fan Zhang, Qimeng Quan, Ying Ma, Xuexun Fang, Kwangmeyung Kim, Seulki Lee, Xiaoyuan Chen.Theranostics. 2011, (1) pp. 18-27. January 12, 2011. http://www.thno.org/v01p0018.htm.

Description

Lipoamido-dPEG®24-acid, product number QBD-10811, is a single molecular weight, discrete PEG (dPEG®) surface modification reagent for metal surfaces, especially gold and silver. The hydrophilic dPEG®24 spacer is 85 atoms (99 Å) long. The lipoamide moiety rapidly forms stable dative bonds with gold or silver. Using a carbodiimide such as EDC and an acylating agent such N-hydroxysuccinimide (NHS), the propionic acid group will react with free amines to form amide bonds. The water-soluble, non-immunogenic dPEG® spacer adds hydrodynamic volume to conjugates made with this product. For circulating nanoparticles, the increased hydrodynamic volume reduces or eliminates opsonization and facilitates a longer circulation time in vivo.

Lipoic acid, also known as thioctic acid and alpha-lipoic acid (ALA), is an organosulfur compound used by cells as an essential cofactor. The sulfur atoms at positions C6 and C8 form a disulfide bond in a five (5)-membered ring. Like other thiol products, lipoic acid readily forms dative bonds with gold, silver, and other metals. Because two dative bonds form for each molecule of lipoic acid, the thiol-metal dative bond is more stable than dative bonds formed with compounds containing one free thiol atom. Lipoic acid exists typically in an oxidized (closed ring) state. It is readily reduced to an open ring state called dihydrolipoic acid (DHLA) using tris(2-carboxyethyl)phosphine (TCEP) or other reducing agents.

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), pp. 188-190, 458-497, 924-935.

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.

Compact Biocompatible Quantum Dots Functionalized for Cellular Imaging. Wenhao Liu, Mark Howarth, Andrew B. Greytak, Yi Zheng, Daniel G. Nocera, Alice Y. Ting, and Moungi G. Bawendi. J. Am. Chem. Soc. 2008, 130 (4) pp 1274–1284. January 5, 2008. DOI: 10.1021/ja076069p.

Description

t-boc-N-amido-dPEG®24-acid, product number QBD-10760, is composed of a boc-protected primary amine and a propionic acid group on opposite ends of an extended (76 atoms), single molecular weight, discrete PEG (dPEG®) linker. Designed for use in Boc-based peptide chemical synthesis, t-boc-N-amido-dPEG®24-acid can be used to insert a discrete PEG linker/spacer at the N-terminus of a peptide chain or to add a dPEG® onto the side chain of an amino acid such as lysine or ornithine. Insertion of t-boc-N-amido-dPEG®24-acid at the N-terminus of a peptide allows the creation of a flexible, hydrophilic bridge to the C-terminus of another peptide. The Boc protecting group cleaves easily under acidic conditions with, for example, TFA. This compound can also be used to modify amine-functionalized surfaces to passivate them with a hydrophilic spacer. Removal of the boc group with acid allows for functionalization of the surface with peptides, proteins, or small molecules.

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

Hydroxy-dPEG®24-t-butyl ester, product number QBD-10722, is a versatile building block based upon a monodispersed polyethylene glycol (PEG) chain. A primary alcohol group terminates one end of the molecule. The opposite end is a propionic acid group protected as the tert-butyl ester. The terminal hydroxy group can be functionalized with various reactive groups to permit direct modification of surfaces, small molecules, or biomolecules. Alternatively, the hydroxy group can react with isothiocyanates or active esters of carboxylic acids to form new conjugates. The tert-butyl ester deprotects with trifluoroacetic acid (TFA) or formic acid, exposing the terminal propionic acid, which can then be activated as the NHS or TFP ester or directly coupled to an amine using a suitable carbodiimide.

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

Lipoamido-dPEG®24-TFP ester, product number QBD-10643, is a single molecular weight, discrete PEG (dPEG®) modification reagent. The product consists of alpha-lipoic acid and a 2,3,5,6-tetrafluorophenyl (TFP) ester on opposite ends of a long (84 atoms) dPEG® spacer. The lipoic acid group forms two (2) coordinate covalent bonds (dative bonds) with metal, especially gold and silver. The TFP ester reacts with free amines to form amide bonds. Applications for this product include peptide or protein immobilization on metal surfaces, the formation of self-assembled monolayers (SAMs) on metal surfaces, and sensor development.

Lipoic acid, also known as α-lipoic acid and thioctic acid, is a naturally occurring antioxidant that functions as a cofactor in several enzyme systems. It consists of a dithiolane ring (a five-membered ring containing a disulfide) attached to a pentanoic acid group. As a bidentate thiol ligand, lipoic acid forms two stable dative bonds per lipoic acid group with gold, silver, and other metals. These dative bonds form with oxidized lipoic acid or reduced dihydrolipoic acid (DHLA). Because it forms two dative bonds on metal surfaces, lipoic acid is more stable than PEGylation reagents containing a single thiol. This increased stability prevents lipoic-acid-functionalized dPEG® products from being oxidized off the metal surface.

When using this product, it is typical to begin with the conjugation of the carboxyl end of the dPEG® to an amino group to form an amide bond. As documented in the scientific literature, TFP esters react more readily with amines and possess better hydrolytic stability than N-hydroxysuccinimidyl (NHS) esters. TFP esters optimally react with amines at pH 7.5 – 8.0.

After reacting the TFP ester end of the molecule, the lipoic acid end of the dPEG® linker can be reacted with metals such as gold or silver. The lipoic acid group forms dative bonds with metals with or without reduction to DHLA. If reduction to DHLA is preferred, Tris(2-carboxyethyl)phosphine (TCEP) will reduce lipoic acid to DHLA rapidly.

Lipoamido-dPEG®24-TFP ester dissolves in water or aqueous buffer and organic solvents. Stock solutions in water or aqueous buffer do not have long-term stability and should be used immediately. For stock solutions with long-term stability, we recommend dry (over 3 Å molecular sieves) water-miscible solvents such as N, N-dimethylacetamide (DMAC) or acetonitrile. Unused stock solutions in dry organic solvents should be stored at -20°C or colder.

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.