Description

DOTA-tris(acid)-amido-dPEG®23-maleimide, product number QBD-11171, links a thiol-reactive maleimide group with the popular, macrocyclic, bifunctional chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) through a long (74 atoms, 85.9 Å), single molecular weight, discrete PEG (dPEG®) linker. The DOTA moiety effectively chelates trivalent radioisotopes of lanthanides and certain rare earth elements like yttrium. The maleimide group reacts chemoselectively with thiols at pH 6.5 – 7.5 in a click chemistry-like reaction. Because the four acetate groups on the macrocycle are unprotected, this DOTA compound should be conjugated to the target molecule at the end of the synthetic process when no further reactions will be carried out. DOTA products are commonly used in radiopharmacy in imaging, diagnostic, and therapeutic applications.

The long, flexible, amphiphilic dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can reduce a conjugate molecule’s renal clearance, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and the increased hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(acid)-amido-dPEG®11-maleimide, product number QBD-11167, links a thiol-reactive maleimide group with the popular, macrocyclic, bifunctional chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) through a medium-length (37 atoms, 43.5 Å), single molecular weight, discrete PEG (dPEG®) linker. The DOTA moiety is designed to chelate trivalent radioisotopes of lanthanides and certain rare earth elements like yttrium. The maleimide group reacts chemoselectively with thiols at pH 6.5 – 7.5 in a click chemistry-like reaction. Because the four acetate groups on the macrocycle are unprotected, this DOTA compound should be conjugated to the target molecule at the end of the synthetic process when no further reactions will be carried out. DOTA products are commonly used in radiopharmacy in imaging, diagnostic, and therapeutic applications.

The medium-length, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can reduce a conjugate molecule’s renal clearance, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and the increased hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(TBE)-amido-dPEG®11-MAL, product number QBD-11166, is a thiol-reactive DOTA compound containing a medium-length (37 atoms, 44.5 Å), single molecular weight, discrete polyethylene glycol (dPEG®) spacer between the DOTA and the maleimide groups. The macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) moiety is protected with tert-butyl ester (TBE) groups on the four acetate units.

DOTA is a popular, effective bifunctional chelator that is used in radiopharmaceutical applications (radioimaging, radiotherapeutics) that require trivalent isotopes of yttrium or lanthanides. This form of DOTA has the four acetate groups protected with tert-butyl esters (TBE). This intermediate DOTA form is not an effective chelator, but it is useful in situations where the DOTA needs to be incorporated into the molecule at an early stage of development. 

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

DOTA-tris(acid)-amido-dPEG®24-TFP ester, product number QBD-11163, contains a DOTA-tris(acid) group conjugated to a long (76 atoms, 88.8 Å), discrete polyethylene glycol (dPEG®) spacer and functionalized with 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts specifically and efficiently with amines at an optimal pH range of 7.5 – 8.0. The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a popular, effective bifunctional chelator of trivalent lanthanide and yttrium radioisotopes. It is used in radiopharmacy for imaging, diagnostic, and therapeutic applications.

The long, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can reduce a conjugate molecule’s renal clearance, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and the increased hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(acid)-amido-dPEG®12-TFP ester, product number QBD-11162, contains a DOTA-tris(acid) group conjugated to a medium-length (40 atoms, 46.3 Å), discrete polyethylene glycol (dPEG®) spacer and functionalized with 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts specifically and efficiently with amines at an optimal pH range of 7.5 – 8.0. The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a popular, effective bifunctional chelator of trivalent lanthanide and yttrium radioisotopes. It is used in radiopharmacy for imaging, diagnostic, and therapeutic applications.

The medium-length, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can reduce a conjugate molecule’s renal clearance, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and the increased hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(acid)-amido-dPEG®4-TFP ester, product number QBD-11160, contains a DOTA-tris(acid) group conjugated to a short (16 atoms, 17.9 Å), discrete polyethylene glycol (dPEG®) spacer and functionalized with 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts specifically and efficiently with amines at an optimal pH range of 7.5 – 8.0. The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a popular, effective bifunctional chelator of trivalent lanthanide and yttrium radioisotopes. It is used in radiopharmacy for imaging, diagnostic, and therapeutic applications.

The short, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can reduce a conjugate molecule’s renal clearance, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and the increased hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(TBE)-amido-dPEG®24-TFP ester, product number QBD-11158, contains a DOTA-tris(TBE) group conjugated to a long (76 atoms, 88.8 Å), discrete polyethylene glycol (dPEG®) spacer and functionalized with 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts specifically and efficiently with amines at an optimal pH range of 7.5 – 8.0.

The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a popular, effective bifunctional chelator used in radiopharmaceutical applications (radioimaging, radiotherapeutics) that require trivalent radioisotopes of yttrium or lanthanides. This form of DOTA has the four acetate groups protected with tert-butyl esters (TBE) and is not an effective chelator. However, it is useful in situations where the DOTA needs to be incorporated into the molecule at an early stage of development. The DOTA moiety becomes an effective chelator after the removal of the TBE protecting groups.

The long, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can act to reduce renal clearance of the conjugate, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and its large hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(TBE)-amido-dPEG®12-TFP ester, product number QBD-11157, contains a DOTA-tris(TBE) group conjugated to a medium-length (40 atoms, 47.1 Å), discrete polyethylene glycol (dPEG®) spacer and functionalized with 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts specifically and efficiently with amines at an optimal pH range of 7.5 – 8.0.

The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a popular, effective bifunctional chelator used in radiopharmaceutical applications (radioimaging, radiotherapeutics) that require trivalent isotopes of yttrium or lanthanides. This form of DOTA has the four acetate groups protected with tert-butyl esters (TBE) and is not an effective chelator. However, it is useful in situations where the DOTA needs to be incorporated into the molecule at an early stage of development. The DOTA moiety becomes an effective chelator after the removal of the TBE protecting groups.

The medium-length, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can act to reduce renal clearance of the conjugate, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and its large hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(TBE)-amido-dPEG®4-TFP ester, product number QBD-11155, contains a DOTA-tris(TBE) group conjugated to a short (16 atoms, 17.8 Å), discrete polyethylene glycol (dPEG®) spacer and functionalized with 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts specifically and efficiently with amines within an optimal pH range of 7.5 – 8.0.

The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a popular, effective bifunctional chelator used in radiopharmaceutical applications (radioimaging, radiotherapeutics) that require trivalent lanthanide isotopes and certain rare earth metals such as yttrium. This form of DOTA has the four acetate groups protected with tert-butyl esters (TBE) and is not an effective chelator. However, it is useful in situations where the DOTA needs to be incorporated into the molecule at an early stage of development. The DOTA moiety becomes an effective chelator after the removal of the TBE protecting groups.

The short, amphiphilic, flexible dPEG® linker between the DOTA and the TFP ester moieties increases the hydrodynamic volume and water solubility of conjugate molecules. The increased hydrodynamic volume can act to reduce renal clearance of the conjugate, thereby increasing serum half-life and reducing the dosage of the conjugate required for efficacy. Moreover, dPEG® is non-immunogenic, and its large hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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

DOTA-tris(TBE)-amido-dPEG®23-bromoacetamide, product number QBD-11153, combines the macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) through a single molecular weight, discrete polyethylene glycol (dPEG®) linker to a thiol-reactive bromoacetyl group that couples to the dPEG® linker via an amide bond. The dPEG® linker contains 75 atoms and is 85.2 Å long from the terminal amide adjacent to the DOTA moiety to the methylene group adjacent to the bromine atom. This product is useful in radioimaging and radiotherapeutic applications.

The bromoacetate moiety (present as the bromoacetamide in QBD-11153) reacts chemoselectively, but not chemospecifically, with free thiol groups to form stable thioether bonds. The rate and specificity of bromoacetate for free thiols depends upon the pH of the reaction and the relative availability (compared to thiols) of other groups with which the bromoacetate moiety can react (for example, surface-accessible amines).

DOTA is a highly popular bifunctional chelator used in a variety of diagnostic and therapeutic applications for the delivery of radionuclides, particularly lanthanide radionuclides and certain rare earth radioisotopes such as yttrium. DOTA is the preferred ligand for treatments using trivalent lanthanides because it binds the metal ions to form thermodynamically stable, kinetically inert complexes. Importantly, this product has the DOTA group protected by three tert-butyl ester groups and cannot chelate metals until those protecting groups are removed (using, for example, trifluoroacetic acid). However, this compound can be introduced at an early stage in a drug development process and left protected until the final step before chelation. This allows users to extensively manipulate and develop the product without putting the DOTA moiety’s performance at risk.

The long, flexible, single molecular weight dPEG® linker between the DOTA and the bromoacetate groups serves many purposes. First, each ethylene glycol unit in the dPEG® chain acquires up to three molecules of water through hydrogen bonding resulting in improved water solubility for conjugate molecules. Second, in aqueous environments such as blood, dPEG® increases the hydrodynamic volume of dPEG® conjugates. With larger hydrodynamic volumes, conjugates are less susceptible to renal excretion, meaning that lower doses of the diagnostic or therapeutic agent are needed for the efficacious performance of the conjugate. Third, dPEG® is non-immunogenic, and its large hydrodynamic volume helps reduce the immunogenicity of conjugated molecules.

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.