MAL-dPEG®₄-NHS ester (QBD-10214)

Description

MAL-dPEG®4-NHS ester, product number QBD-10214, is a crosslinking reagent that joins a sulfhydryl to a free amine. 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 (dPEG®) chain.

The reactions that join free amines to free thiols are among the most popular, most useful crosslinking reactions in bioconjugate chemistry. These reactions require heterobifunctional reagents that bridge the two different reactive groups. Traditional crosslinkers are hydrophobic molecules, but our dPEG® crosslinking products are single molecular weight PEG compounds with discrete chain lengths.

The conjugation of conventional hydrophobic crosslinking reagents to biomolecules almost inevitably triggers problems such as aggregation and precipitation of the conjugates. These problems do not occur with our water-soluble, non-immunogenic dPEG® crosslinkers.
With these crosslinkers, the NHS ester end of the molecule must conjugate to a target molecule before the maleimide end of the molecule. At pH 7.0 – 7.5, NHS esters react optimally with free amines. However, NHS esters can react with free amines with pH as low as 6.0. As the pH increases, the hydrolysis rate of the ester increases. Thus, we strongly discourage storing MAL-dPEG®4-NHS ester in water or aqueous buffers. Instead, we recommend that customers make new solutions of the product as needed, use them immediately, and discard unused solutions after use.

The reaction of the maleimide end of MAL-dPEG®4-NHS ester, QBD-10214, with a sulfhydryl proceeds optimally at pH 6.5 – 7.5. Use the lowest reasonable pH within this range. Above pH 7.5, free amines compete with free thiols at the maleimide reaction site, which can cause confusing results. Moreover, at higher pH values, the maleimide ring may open to form unreactive maleamic acid.
Numerous scientific papers, patents, and presentations have published the uses of MAL-dPEG®4-NHS ester, QBD-10214. The following list highlights some of the more important uses of this product:
Development of therapeutic antisense drugs;
Development of active and passively targeted nanoparticles;
Development of vaccines;
Development of nanoparticle-based photodynamic therapy;
Development of Gd-doped CuS nanoparticles for imaging and targeted photothermal treatment of gastric tumors;
Development of antibody-drug conjugates;
Development of extracellular antibody-drug conjugates; and,
Development of multiplex assays.

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); 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.

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.

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Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis. Eric A. Murphy, Bharat K. Majeti, Leo A. Barnes, Milan Makale, Sara M. Weis, Kimberly Lutu-Fuga, Wolfgang Wrasidlo, David A. Cheresh. PNAS. 2008, 105 (27) pp 9343-9348. July 8, 2008. DOI: 10.1073/pnas.0803728105.

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Therapy of Murine Pulmonary Aspergillosis with Antibody-Alliinase
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Maize rayado fino virus virus-like particles expressed in tobacco plants: A new platform for cysteine selective bioconjugation peptide display. Angela Natilla, Rosemarie W. Hammond. Journal of Virological Methods. 2011, 178 (1-2) pp 209-215. September 22, 2011. DOI: 10.1016/j.jviromet.2011.09.013.

Transfection efficiency of depolymerized chitosan and epidermal growth factor conjugated to chitosan–DNA polyplexes. Sasamon Supaprutsakul, Wilaiwan Chotigeat, Supreya Wanichpakorn, Ureporn Kedjarune-Leggat. Journal of Materials Science- Materials in Medicine. 2010, 21 (5) pp 1553-1561. May 1, 2010. DOI: 10.1007/s10856-010-3993-9.

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA. International Journal of Nanomedicine. 2013, 8 pp 2041–2052. May 20, 2013. DOI: 10.2147/IJN.S43683.

Surface Coating Directed Cellular Delivery Of TAT-Functionalized Quantum Dots. Yifeng Wei, Nikhil R. Jana, Shawn J. Tan, and Jackie Y. Ying. Bioconjugate Chem. 2009, 20 (9) pp1752-1758. August 14, 2009. DOI: 10.1021/bc8003777.

Targeted nanogels: a versatile platform for drug delivery to tumors. Eric A. Murphy, Bharat K. Majeti, Rajesh Mukthavaram, Lisette M. Acevedo,Leo A. Barnes, and David A. Cheresh. Molecular Cancer Therapeutics. 2011, 10 (6) pp 972-982. April 25, 2011. DOI: 10.1158/1535-7163.MCT-10-0729.

To Target or Not to Target: Active vs. Passive Tumor Homing of Filamentous Nanoparticles Based on Potato virus X. Sourabh Shukla, Nicholas A. DiFranco, Amy M. Wen and Nicole F. Steinmetz. Cellular and Molecular Bioengineering. 2015, pp 1-24. April 8, 2015. DOI: 10.1007/s12195-015-0388-5.

Biocompatible and biodegradable fibrinogen microshperes for tumor-targeted doxorubicin delivery. Jae Yeon Joo, GilYong Park, and Seong Soo A An. International Journal of Nanomedicine. 2015, 10 pp 101-111. September 1, 2015. DOI: 10.2147/IJN.S88381.

Controlled co-reconstitution of multiple membrane proteins in lipid bilayer nanodiscs using DNA as a scaffold. Thomas Raschle, Chenxiang Lin, Ralf Jungmann, William M. Shih, and Gerhard Wagner. ACS Chemical Biology. 2015, pp 1-18. September 10, 2015. DOI: 10.1021/acschembio.5b00627.

Serum albumin ‘camouflage’ of plant virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics. Andrzej S. Pitek, Slater A. Jameson, Frank A. Veliz, Sourabh Shukla, and Nicole F. Steinmetz. Biomaterials. 2016, 89 pp 89-97, February 23, 2016. DOI: 10.1016/j.biomaterials.2016.02.032.

Biogenic and Synthetic Peptides with Oppositely Charged Amino Acids as Binding Sites for Mineralization. Marie-Louise Lemloh, Klara Altintoprak, Christina Wege, Ingrid M Weiss, and Dirk Rothenstein. Materials. 2017, 10 (119) pp 1-15. January 28, 2017. DOI: 10.3390/ma10020119.

Affinity-Based Assembly of Peptides on Plasmonic Nanoparticles Delivered Intracellularly with Light Activated Control. Demosthenes P Morales, William Wonderly, Xiao Huang, Meghan McAdams, Amanda Chron, and Norbert O Reich. Bioconjugate Chemistry. 2017, pp 1-6. May 19, 2017. DOI: 10.1021/acs.bioconjchem.7b00276.

Elongated plant virus-based nanoparticles for enhanced delivery of thrombolytic therapies. Andrzej Stanislaw Pitek, Yunmei Wang, Sahil Gulati, Huiyun Gao, Phoebe L Stewart, Daniel I. Simon, and Nicole F Steinmetz. Molecular Pharmaceutics. 2017, pp 1-9. September 7, 2017. DOI: 10.1021/acs.molpharmaceut.7b00559.

Magnetic Semiconductor Gd-Doping CuS Nanoparticles as Activatable Nanoprobes for Bimodal Imaging and Targeted Photothermal Therapy of Gastric Tumors. Hua Sh , Yidan Sun, Runqi Yan, Shunli Liu, Li Zhu, Song Liu, Yuzhang Feng, Peng Wang, Jian He, Zhengyang Zhou, and Deju Ye. Nano Letters. 2019. January 28, 2019. DOI: 10.1021/acs.nanolett.8b04179

A Viral Nanoparticle Cancer Vaccine Delays Tumor Progression and Prolongs Survival in a HER2+ Tumor Mouse Model. Sourabh Shukla, Michal Jandzinski, Chao Wang, Xingjian Gong, Kristen Weber Bonk, Ruth A. Keri, Nicole F. Steinmetz. 2019. January 29, 2019. https://doi.org/10.1002/adtp.201800139.

Let There Be Light: Targeted Photodynamic Therapy Using High Aspect Ratio Plant Viral Nanoparticles. Paul L. Chariou, Lu Wang, Cian Desai, Jooneon Park, Leanna K. Robbins, Horst A. von Recum, Reza A. Ghiladi, Nicole F. Steinmetz. Cancer Phototherapy. 2019. https://doi.org/10.1002/mabi.201800407

Reductively cleavable polymer-drug conjugates based on dendritic polyglycerol sulfate and monomethyl auristatin E as anticancer drugs. Nadine Rades, Katharina Achazi, Min Qiu, Chao Deng, Rainer Haag, Zhiyuan Zhong, Kai Licha. Journal of Controlled Release. 2019. 300 (2019) pp 13-21. February 19, 2019. doi.org/10.1016/j.jconrel.2019.01.035

Improved in vivo targeting of BCL-2 phenotypic conversion through hollow gold nanoshell delivery. Erin Morgan, John T. Gamble, Martin C. Pearce, Daniel J. Elson, Robert L. Tanguay, Siva Kumar Kolluri, Norbert O. Reich. Apoptosis. 2019, Volume 24, Issue 5-6, pp 529-537. March 16, 2019. DOI: https://doi.org/10.1007/s10495-019-01531-1

Active Targeting of Dendritic Polyglycerols for Diagnostic Cancer Imaging. Kritee Pant, Christin Neuber, Kristof Zarschler, Johanna Wodtke, Sebastian Meister, Rainer Haag, Jens Pietzsch, Holger Stephan. Small, 2019, 1095013. December 26, 2019. DOI: 10.1002/smll.201905013

An Antibody-Immobilized Silica Inverse Opal Nanostructure for Label-Free Optical Biosensors. Wang Sik Lee, Taejoon Kang, Shin-Hyun Kim and Jinyoung Jeong. Sensors 2018, 18(1), 307; January 20, 2018. https://doi.org/10.3390/s18010307

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA. Meenakshi Malhotra, Catherine Tomaro-Duchesneau, Shyamali Saha, Imen Kahouli, Satya Prakash. PubMed Central®. 2013. Volume 8. May 21, 2013.

An Investigation of Phosphorous-Based Bioconjugation Techniques for Protein Modification. Maja Lopandic. UWSPACE. 2022. April 7, 2022. http://hdl.handle.net/10012/18138.

TLR agonists induce sustained IgG to hemagglutinin stem and modulate T cells following newborn vaccination. Elene A. Clemens, Beth C. Holbrook, Brendan McNeilly, Masaru Kanekiyo, Barney S. Graham & Martha A. Alexander-Miller. npj Vaccines volume 7, Article number: 102 (2022). 08/29/22. https://doi.org/10.1038/s41541-022-00523-8