Description

Hydroxy-dPEG®6-t-butyl ester, product number QBD-10717, 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

MAL-dPEG®6-TFP ester, product number QBD-10556, is a crosslinking reagent that joins free amines to free thiols (sulfhydryl groups) across a medium-length (28 atoms), single molecular weight, discrete PEG (dPEG®) linker. The sulfhydryl groups react with a maleimido group via a Michael addition reaction. The amines form amide bonds with the crosslinker by nucleophilic substitution of the 2,3,5,6-tetrafluorophenyl (TFP) ester of the terminal propionic acid group.

The conjugation of free amines to free thiols is one of the most popular, most useful crosslinking reactions in bioconjugate chemistry is the conjugation of free amines to free thiols. These reactions require heterobifunctional reagents that bridge the two groups. Typical crosslinkers are hydrophobic. Vector Laboratories’ dPEG® crosslinking products are water-soluble, amphiphilic, single molecular weight PEG compounds with discrete chain lengths. These hydrophilic, non-immunogenic, dPEG® crosslinkers prevent the problems with aggregation that arise when using traditional, hydrophobic crosslinkers.

Published studies have shown that TFP esters are more hydrolytically stable in aqueous buffers than N-hydroxysuccinimidyl (NHS) esters and are more reactive toward free amines. TFP esters react under the same conditions as NHS esters. However, the optimal pH range for TFP esters (7.5 – 8.0) is slightly higher than for NHS esters (7.0 – 7.5). Amide bond formation between the TFP-activated propionic acid group of MAL-dPEG®6-TFP ester and a free amine will be slightly slower at a suboptimal pH compared to the reaction rate within the optimum pH range.

The maleimide end of MAL-dPEG®6-TFP ester, product number QBD-10556, reacts optimally with a sulfhydryl at pH 6.5 – 7.5. Conduct the conjugation at the lowest reasonable pH within this range. Above pH 7.5, free amines compete with free thiols at the maleimide reaction site, which may confound the data. Moreover, at higher pH values, the maleimide ring may open to form unreactive maleamic acid.

MAL-dPEG®6-TFP ester, product number QBD-10556, can be used the same way and in the same applications as the equivalent NHS esters. Possible uses for this product include the following:
Coating nanoparticle surfaces;
Tethering antibodies to atomic force microscopy (AFM) probes;
Constructing antibody-drug conjugates (ADCs);
Adding flexibility and water solubility to a peptide;
Increasing the water solubility and hydrodynamic volume of hydrophobic biomolecules;
Building supramolecular constructs; and,
Conjugating the TFP ester end of the molecule a liposomal surface and then using the free maleimide end of the molecule to attach a small molecule drug, peptide, or antibody for targeted delivery of a diagnostic or therapeutic package.

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

Amino-dPEG®6-acid, product number QBD-10067, is a PEGylated amino acid consisting of a primary amine and a propionic acid on opposite ends of a polyethylene glycol (PEG) spacer. The flexible PEG spacer is discrete (Ð = 1), having a single chain length and molecular weight. Moreover, it is highly hydrophilic, increasing the hydrodynamic volume and imparting water solubility to conjugates that incorporate it. Furthermore, Amino-dPEG®6-acid is helpful in wide-ranging applications, including peptide synthesis, surface modification, dendrimer construction, and small molecule modification.

Specifications

Documents

References

1. 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.

2. 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.

3. 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. Dec. 3, 2009. DOI: 10.1021/jm900899g.

4. TNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells. Jaehee Kim, Juhyun Oh, Hannah M Peterson, Jonathan C T Carlson, Mikael J Pittet, Ralph Weissleder. Advanced Biology. 2022. Volume 6, Issue 8. June 8, 2022. https://doi.org/10.1002/adbi.202200030

Description

CBZ-N-amido-dPEG®6-acid, product number QBD-10066, is a benzyl carbamate (Cbz) N-protected amino-dPEG®-acid that provides a short, single molecular weight discrete PEG (dPEG®) spacer. It can be used in peptide synthesis as well as in many other reactions. In peptide synthesis, removal of the Cbz protecting group is orthogonal to many other protecting groups.

Specifications

Documents

References

1. 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®6-acid, product number QBD-10065, is a crosslinker that joins sulfhydryl groups to free amines through a single molecular weight, discrete length polyethylene glycol (dPEG®) chain. The maleimidopropyl moiety reacts with sulfhydryl groups via a Michael addition reaction. The propionic acid terminus of the molecule reacts directly with free amines using EDC or another carbodiimide to form amide bonds. Alternatively, activation of the propionic acid group with N-hydroxysuccinimide (NHS), 2,3,5,6-tetrafluorophenol (TFP), or some other acylating agent permits amide bond formation under mild, controlled conditions.

Specifications

Documents

References

1. 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, and the specific sample protocol for SMCC or sulfo-SMCC on pp. 283-286.
2. 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®6-NHS ester, product number QBD-10064, is a crosslinking reagent that joins a sulfhydryl to a free amine across 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 short, discrete-length polyethylene glycol chain (dPEG®).

Specifications

Documents

References

1. 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.
2. 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.
3. Direct Cell Surface Modification with DNA for the Capture of Primary Cells and the Investion of Myotube Formation on Defined Patterns. Sonny C. Haiso, Betty J. Shaun, Hiroaki Onoe, Erik S. Douglas, Zev J. Gartner, Richard A. Mathies, Carolyn R. Bertozzi, and Matthew B. Francis. Langmuir. 2009, 25 (12), pp 6985–6991. April 29, 2009. DOI: 10.1021/la900150n.
4. A sandwich-type DNA array platform for detection of GM targets in multiplex assay. Sena Cansız, Can Ozen, Ceren Bayrac, A. Tahir Bayrac, Fatma Gul, Murat Kavruk, Remziye Yılmaz, Fusun Eyidogan, Huseyin, Avni Oktem. European Food Research and Technology. 2012, 235 (3) pp 429-437. July 6, 2012. DOI:10.1007/s00217-0121767y.
5. A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose. Laura E. Richert, Amy E. Servidb, Ann L. Harmsen, Agnieszka Rynda-Apple, Soo Han, James A. Wiley, Trevor Douglas, Allen G. Harmsen. Vaccine. 2012, 30 (24) pp 3653-3665. May 21, 2012. DOI: 10.1016/j.vaccine.2012.03.035.
6. New Assay for Quantification of PEGylated Proteins During in Vitro Permeability Studies. Spela Jalen,Vanja Smilovic, Katarina Fidler, Barbara Podobnik, Maja Marusic, Radovan Komel, Vladka Gaberc-Porekar and Simona Jevsevar. Acta Chimica Slovenica. 2014, 61 (3) pp 615-622. January 15, 2014.
7. Optimization, Production and Characterization of a CpG-Oligonucleotide-Ficoll Conjugate Nanoparticle Adjuvant for Enhanced Immunogenicity of Anthrax Protective Antigen. Bob Milley, Radwan Kiwan, Gary S. Ott, Carlo Calacsan, Melissa Kachura, John D Campbell, Holger Kanzler, and Robert L. Coffman. Bioconjugate Chemistry. 2016, April 13, 2016. DOI: 10.1021/acs.bioconjchem.6b00107.
8. Immune Response Modulation of Conjugated Agonists with Changing Linker Length. Keun Ah Ryu, Katarzyna Slowinska, Troy Moore, and Aaron Esser-Kahn. ACS Chemical Biology. 2016, October 17, 2016. DOI: 10.1021/acschembio.6b00895.
9. Surface Coating of Nanoparticles Reduces Background Inflammatory Activity while Increasing Particle Uptake and Delivery. Brittany A Moser, Rachel C Steinhardt, and Aaron P Esser-Kahn. ACS Biomaterials Science and Engineering. 2016. December 1, 2016. DOI: 10.1021/acsbiomaterials.6b00473.
10. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human. Miklos Fagyas, Katalin Uri, Ivetta M. Siket, Gabor A. Fulop, Viktoria Csato, Andrea Darago, Judit Boczan, Emese Banyai, Istvan Elek Szentkiralyi, Tamas Miklos Maros, Tamas Szerafin, Istvan Edes, Zoltan Papp, Attila Toth. PLoS ONE. 2014, 9 (4) e87844. April, 1 2014. DOI: 10.1371/journal.pone.0087844.

Description

Fmoc-N-amido-dPEG®6-acid, product number QBD-10063, is one of a broad line of products designed for use in peptide synthesis. The short (22 atoms), discrete PEG (dPEG®) spacer is functionalized with a propionic acid group on one end and Fmoc-protected amine on the other. The product can be added to the N-terminus of a growing peptide chain or to a primary-amine-functionalized side chain of an amino acid such as lysine. The dPEG®6 spacer imparts water solubility to the peptide to which it is conjugated.

QBD-10063 permits our customers to insert a dPEG® spacer into a peptide chain using familiar Fmoc chemistry using solid phase or solution phase chemistry. The dPEG® compound can be inserted at either end of the peptide chain or in the middle of two amino acid sequences to provide a flexible linker between distinct functional peptides. Additionally, the dPEG® spacer can be used to provide spacing in a synthetic construct where steric hindrance is a problem. The amphiphilic nature of dPEG® products means that the construct gains hydrodynamic volume and water solubility while remaining soluble in organic solvent. The Fmoc protecting group removes easily with a solution of piperidine in N,N-dimethylformamide (DMF).

Specifications

Documents

References

1. 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.
2. Polyproline-Rod Approach to Isolating Protein Targets of Bioactive Small Molecules: Isolation of a New Target of Indomethacin. Shin-ichi Sato, Youngjoo Kwon, Shinji Kamisuki, Neeta Srivastava, Quian Mao, Yoshinori Kawazoe, and Motonari Uesugi. J. Am. Chem. Soc. 2007, 129 (4), pp 873–880. January 4, 2007. DOI: 10.1021/ja0655643.
3. Design and Synthesis of Multifunctional Gold Nanoparticles Bearing Tumor-Associated Glycopeptide Antigens as Potential Cancer Vaccines. Raymond P. Brinãs, Andreas Sundgren, Padmini Sahoo, Susan Morey, Kate Rittenhouse-Olson, Greg E. Wilding, Wei Deng, and Joseph J. Barchi, Jr. Bioconjugate Chem. 2012, 23 (8), pp 1513-1523. July 19, 2012. DOI: 10.1021/bc200606s.
4. Mechanistic Studies of a Peptidic GRP78 Ligand for Cancer Cell-Specific Drug Delivery. Ying Liu, Sebastian C.J. Steiniger, YoungSoo Kim, Gunnar F. Kaufmann, Brunhilde Felding-Habermann, and Kim D. Janda. Molecular Pharmaceutics 2007 4(3) p 435-447. January 2007. DOI:10.1021/mp060122j.
5. Multifunctional nanoparticles as simulants for a gravimetric Immunoassay. Scott A. Miller, Leslie A. Hiatt, Robert G. Keil, David W. Wright, and David E. Cliffel. Analytical and Bioanalytical Chemistry. 2011, 399 (3) pp 1021-1029 January 1, 2011. DOI:10.1007/s00216-010-4419-8.
6. Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA). Duanwen Shen, Fei Xie, W. Barry Edwards. PLoS ONE. 2013, 8 (7), pp e68339. July 25, 2013. DOI: 10.1371/journal.pone.0068339.
7. A Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes. Jared F. Stefanick, Jonathan D. Ashley, Tanyel Kiziltepe, and Basar Bilgicer. ACS Nano. 2013, 7 (4) pp 2935–2947. February 19, 2013. DOI: 10.1021/nn305663e.
8. Enhanced Cellular Uptake of Peptide-Targeted Nanoparticles through Increased Peptide Hydrophilicity and Optimized Ethylene Glycol Peptide-Linker Length. Jared F. Stefanick, Jonathan D. Ashley, and Basar Bilgicer. ACS Nano. 2013, 7 (9) pp 8115–8127. August 29, 2013. DOI: 10.1021/nn4033954.
9. Novel Monodisperse PEGtide Dendrons: Design, Fabrication, and Evaluation of Mannose Receptor-Mediated Macrophage Targeting. Jieming Gao, Peiming Chen, Yashveer Singh, Xiaoping Zhang, Zoltan Szekely, Stanley Stein, and Patrick J. Sinko. Bioconjugate Chem. 2013, 24 (8) pp 1332–1344. June 29, 2013. DOI: 10.1021/bc400011v.
10. B-Peptide Conjugates: Syntheses and CD and NMR Investigations of B/a-Chimeric Peptides, of a DPA-B-Decapeptide, and of a PEGylated b-Heptapeptide. James Gardiner, Raveendra I. Mathad, Berhard Jaun, Jurg V. Schreiber, Oliver Flogel, and Dieter Seebach. Helvetica Chimica Acta. 2009, 92 (12) pp 2698-2721. December 17, 2009. DOI: 10.1002/hlca.200900325.
11. Immunomodulation of the NLRP3 Inflammasome through Structure-Based Activator Design and Functional Regulation via Lysosomal Rupture. Saikat Manna, William J. Howitz, Nathan J. Oldenhuis, Alexander C. Eldredge, Jingjing Shen, Fnu Naorem Nihesh, Melissa B. Lodoen, Zhibin Guan, and Aaron P. Esser-Kahn. ACS Central Science. 2018, 4, pp 982-995. July 2, 2018. DOI: 10.1021/acscentsci.8b00218.
12. PEG-Peptide Conjugates. Ian W Hamley. Biomacromolecules. 2014. April 1, 2014. DOI: 10.1021/bm500246w.
13. Site-Dependent Degradation of a Non-Cleavable Auristatin-Based Linker-Payload in Rodent Plasma and Its Effect on ADC Efficacy. Magdalena Dorywalska, Pavel Strop, Jody A. Melton-Witt, Adela Hasa-Moreno, Santiago E. Farias, Meritxell Galindo Casas, Kathy Delaria, Victor Lui, Kris Poulsen, Janette Sutton, Gary Bolton, Dahui Zhou, Ludivine Moine, Russell Dushin, Thomas-Jaume Pons, Arvind Rajpal. Plos One. 2015, 10 (7) e0132282. July 10, 2015. DOI: 10.1371/journal.pone.0132282.
14. A Synthetic Virus-Like Particle Streptococcal Vaccine Candidate Using B-Cell Epitopes from the Proline-Rich Region of Pneumococcal Surface Protein A. Marco Tamborrini, Nina Geib, Aniebrys Marrero-Nodarse, Maja Jud, Julia Hauser, Celestine Aho, Araceli Lamelas, Armando Zuniga, Gerd Pluschke, Arin Ghasparian and John A. Robinson. Vaccines. 2015, 3 (4), pp 850-874, October 16, 2015. DOI: 10.3390/vaccines3040850.
15. Nanoallergens: A multivalent platform for studying and evaluating potency of allergen epitopes in cellular degranulation. Peter E Deak, Maura R Vrabel, Vincenzo J Pizzuti, Tanyel Kiziltepe, and Basar Bilgicer. Experimental Biology and Medicine. 2016, 0 pp 1-11. April 13, 2016. DOI: 10.1177/1535370216644533.
16. Control of strand registry by attachment of PEG chains to amyloid peptides influences nanostructure. Valeria Castelletto, Ge Cheng, Steve Furzeland, Derek Atkinsb and Ian W. Hamley. Soft matter. 2012, 8, pp 5434-5438. April 16, 2012. DOI:10.1039/C2SM25546D.
17. Optimizing design parameters of a peptide targeted liposomal nanoparticle in an in vivo multiple myeloma disease model after initial evaluation in vitro. Jared F. Stefanick, David T. Omstead, Jonathan D. Ashley, Peter E. Deak, Nur Mustafaoglu, Tanyel Kiziltepe, Basar Bilgicer. Journal of Controlled Releases. 2019, 311-312 pp 190-200. August 29, 2019. https://doi.org/10.1016/j.jconrel.2019.08.033.
18. Engineering peptide-targeted liposomal nanoparticles optimized for improved selectivity for HER2-positive breast cancer cells to achieve enhanced in vivo efficacy. Baksun Kim, Jaeho Shin, Junmin Wu, David T. Omstead, Tanyel Kiziltepe, Laurie E. Littlepage, Basar Bilgicer. Journal of Controlled Release. 2020. Volume 322, 10 June 2020, Pages 530-541. April 8, 2020. DOI: 10.1016/j.jconrel.2020.04.010
19. High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro. Rajini Nagaraj, Trevor Stack, Sijia Yi, Benjamin Mathew, Kenneth R Shull, Evan A Scott, Mathew T Mathew and Divya Rani Bijukumar.Nanomaterials 2020, 10(3), 581;March 22, 2020. DOI: 10.3390/nano10030581
20. Efficient capture of circulating tumor cells with low molecular weight folate receptor-specific ligands. Yingwen Hu, Danyang Chen, John V Napoleon, Madduri Srinivasarao, Sunil Singhal, Cagri A Savran, Philip S Low. Scientific Reports. 2022. May 20, 2022. https://doi.org/10.1038/s41598-022-12118-3

Description

Amino-dPEG®6–t-butyl ester product number QBD-10061, is a single molecular weight, discrete length polyethylene glycol (dPEG®) compound useful for modifying peptides, proteins, and small molecules and for bioconjugation or supramolecular construction. The primary amine group on one end of the dPEG® chain reacts with carboxylic acids to form stable amide bonds. A tert-butyl ester group on the opposite end protects the amine-reactive carboxylic acid.

Trifluoroacetic acid (TFA) effectively removes the protecting group, leaving the propionic acid moiety ready for further reaction.

Specifications

Documents

References

1. 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.