Bissulfosuccinimidyl suberate

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Bissulfosuccinimidyl suberate
Bissulfosuccinimidyl suberate.png
Names
IUPAC name
1-[8-(2,5-Dioxo-3-sulfopyrrolidin-1-yl)oxy-8-oxooctanoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid
Other names
Disulfosuccinimidyl suberate; Bis(sulfosuccinimidyl)suberate; BS3
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.110.895 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C16H20N2O14S2/c19-11-7-9(33(25,26)27)15(23)17(11)31-13(21)5-3-1-2-4-6-14(22)32-18-12(20)8-10(16(18)24)34(28,29)30/h9-10H,1-8H2,(H,25,26,27)(H,28,29,30) X mark.svgN
    Key: VYLDEYYOISNGST-UHFFFAOYSA-N X mark.svgN
  • InChI=1/C16H20N2O14S2/c19-11-7-9(33(25,26)27)15(23)17(11)31-13(21)5-3-1-2-4-6-14(22)32-18-12(20)8-10(16(18)24)34(28,29)30/h9-10H,1-8H2,(H,25,26,27)(H,28,29,30)
    Key: VYLDEYYOISNGST-UHFFFAOYAE
  • C1C(C(=O)N(C1=O)OC(=O)CCCCCCC(=O)ON2C(=O)CC(C2=O)S(=O)(=O)O)S(=O)(=O)O
Properties
C16H20N2O14S2
Molar mass 528.46 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Bissulfosuccinimidyl suberate (BS3) is a crosslinker used in biological research. It is a water-soluble version of disuccinimidyl suberate. [1]

Contents

Crosslinkers

Crosslinkers are chemical reagents that play a crucial role in the preparation of conjugates used in biological research particularly immuno-technologies and protein studies. Crosslinkers are designed to covalently interact with molecules of interest, resulting in conjugation. [2] A spacer arm, generally consisting of several atoms, separates the two molecules, and the nature and length of this spacer is important to consider when designing an assay involving the selected crosslinker. Bissulfosuccinimidyl suberate is an example of a homobifunctional crosslinker. [3]

Characteristics

Water-soluble: BS3 is hydrophilic due to its terminal sulfonyl substituents and as a result dissociates in water, eliminating the need to use organic solvents which interfere with protein structure and function. [4] Because organic solvents need not be used when BS3 is used as the crosslinker, it is ideal for investigations into protein structure and function in physiologic conditions. [5] [3]

Non-cleavable: The BS3 crosslinker has an 8-atom spacer is non-cleavable and the molecule is not cell membrane permeable. BS3 binds irreversibly to its conjugate molecules, meaning that once BS3 creates covalent linkages to its target molecules, those associations are not easily broken. [6]

Membrane impermeable: Since BS3 is a charged molecule, it cannot freely pass through cellular membranes which makes it an ideal crosslinker for cell surface proteins. [7]

Homobifunctional: BS3 is a homobifunctional crosslinker in that it has two identical reactive groups, i.e. the N-hydroxysulfosuccinimide (sulfo-NHS) esters, and only one step is necessary to establish crosslinking between conjugate molecules. [8]

Amine reactive: BS3 is amine-reactive in that its N-hydroxysulfosuccinimide (NHS) esters at each end react specifically with primary amines to form stable amide bonds in a nucleophilic acyl substitution-type reaction in which the N-hydroxysulfosuccinimide acts as the leaving group. [9] BS3 is particularly useful in protein-related applications in that it can react with the primary amines on the side chain of lysine residues and the N-terminus of polypeptide chains. [10] This crosslinker can also be used to stabilize protein-protein interactions for further analysis by immunoprecipitation [11] or crosslinking mass spectroemtry. [12]

Deuterated BS3

The deuterated crosslinker bis(sulfosuccinimidyl) 2,2,7,7-suberate-d4 is the "heavy" BS3 crosslinking agent that contains 4 deuterium atoms. When used in mass spectrometry studies, BS3-d4 provides a 4 dalton shift compared to crosslinked proteins with the non-deuterated analog (BS3-d0). [13] Thus, "heavy" and "light" crosslinker analogs can be used for isotopically labeling protein and peptides in mass spectrometry research applications. [14]

Applications

Disuccinimidyl suberate

Disuccinimidyl suberate (DSS) is the non-water-soluble analog of BS3. DSS and BS3 express the same crosslinking ability toward primary amines. [16] The major structural difference between these two molecules is that DSS does not contain the sulfonate substituents at either end of the molecule, and it is this difference that is responsible for the uncharged, non-polar nature of the DSS molecule. [17] Due to the hydrophobic nature of this crosslinker it must be dissolved in an organic solvent such as dimethylsulfoxide before being added to an aqueous sample. Because of the ability of DSS to cross cell membranes, it is best suited for applications where intracellular crosslinking is needed. [18]

Chemical structure of disuccinimidyl suberate Disuccinimidyl suberate.png
Chemical structure of disuccinimidyl suberate

References

  1. ↑ Shi, Jing-Ming; Pei, Jie; Liu, En-Qi; Zhang, Lin (2017). "Bis(sulfosuccinimidyl) suberate (BS3) crosslinking analysis of the behavior of amyloid-β peptide in solution and in phospholipid membranes". PLOS ONE. 12 (3): e0173871. Bibcode:2017PLoSO..1273871S. doi: 10.1371/journal.pone.0173871 . ISSN   1932-6203. PMC   5360245 . PMID   28323849.
  2. ↑ Arora, Bharti; Tandon, Rashmi; Attri, Pankaj; Bhatia, Rohit (2017). "Chemical Crosslinking: Role in Protein and Peptide Science". Current Protein & Peptide Science. 18 (9): 946–955. doi:10.2174/1389203717666160724202806. ISSN   1875-5550. PMID   27455969.
  3. 1 2 Shao, Jiahui (2016), "Spacer Arm Length" , in Drioli, Enrico; Giorno, Lidietta (eds.), Encyclopedia of Membranes, Berlin, Heidelberg: Springer, pp. 1805–1806, doi:10.1007/978-3-662-44324-8_1244, ISBN   978-3-662-44324-8 , retrieved 2022-12-31
  4. ↑ Verma, Vishal; Rico-Martinez, Roberto; Kotra, Neel; King, Laura; Liu, Jiumeng; Snell, Terry W.; Weber, Rodney J. (2012-10-16). "Contribution of water-soluble and insoluble components and their hydrophobic/hydrophilic subfractions to the reactive oxygen species-generating potential of fine ambient aerosols". Environmental Science & Technology. 46 (20): 11384–11392. Bibcode:2012EnST...4611384V. doi:10.1021/es302484r. ISSN   1520-5851. PMID   22974103.
  5. ↑ Ukai, H.; Inui, S.; Takada, S.; Dendo, J.; Ogawa, J.; Isobe, K.; Ashida, T.; Tamura, M.; Tabuki, K.; Ikeda, M. (1997). "Types of organic solvents used in small- to medium-scale industries in Japan; a nationwide field survey". International Archives of Occupational and Environmental Health. 70 (6): 385–392. Bibcode:1997IAOEH..70..385U. doi:10.1007/s004200050233. ISSN   0340-0131. PMID   9439984. S2CID   46697306.
  6. ↑ Dorywalska, Magdalena; Strop, Pavel; Melton-Witt, Jody A.; Hasa-Moreno, Adela; Farias, Santiago E.; Galindo Casas, Meritxell; Delaria, Kathy; Lui, Victor; Poulsen, Kris; Sutton, Janette; Bolton, Gary; Zhou, Dahui; Moine, Ludivine; Dushin, Russell; Tran, Thomas-Toan (2015). "Site-Dependent Degradation of a Non-Cleavable Auristatin-Based Linker-Payload in Rodent Plasma and Its Effect on ADC Efficacy". PLOS ONE. 10 (7): e0132282. Bibcode:2015PLoSO..1032282D. doi: 10.1371/journal.pone.0132282 . ISSN   1932-6203. PMC   4498778 . PMID   26161543.
  7. ↑ Cooper, Geoffrey M. (2000). "Cell Membranes". The Cell: A Molecular Approach. 2nd Edition. 2 (1) – via National Library of Medicine.
  8. ↑ Webb, Ian K.; Mentinova, Marija; McGee, William M.; McLuckey, Scott A. (2013). "Gas-phase intramolecular protein crosslinking via ion/ion reactions: ubiquitin and a homobifunctional sulfo-NHS ester". Journal of the American Society for Mass Spectrometry. 24 (5): 733–743. Bibcode:2013JASMS..24..733W. doi:10.1007/s13361-013-0590-4. ISSN   1879-1123. PMC   3644013 . PMID   23463545.
  9. ↑ Miller, B. T.; Collins, T. J.; Rogers, M. E.; Kurosky, A. (1997). "Peptide biotinylation with amine-reactive esters: differential side chain reactivity". Peptides. 18 (10): 1585–1595. doi:10.1016/s0196-9781(97)00225-8. ISSN   0196-9781. PMID   9437720. S2CID   34633991.
  10. ↑ Abello, Nicolas; Kerstjens, Huib A. M.; Postma, Dirkje S.; Bischoff, Rainer (November 15, 2007). "Selective acylation of primary amines in peptides and proteins". Journal of Proteome Research. 6 (12): 4770–4776. doi:10.1021/pr070154e. ISSN   1535-3893. PMID   18001078.
  11. ↑ Tang, Xiaoting; Bruce, James E. (2009). "Chemical Cross-Linking for Protein–Protein Interaction Studies". Mass Spectrometry of Proteins and Peptides. Methods in Molecular Biology. Vol. 492. pp. 283–293. doi:10.1007/978-1-59745-493-3_17. ISBN   978-1-934115-48-0. ISSN   1064-3745. PMID   19241040.
  12. ↑ Chen, Zhuo Angel; Rappsilber, Juri (2023-06-01). "Protein structure dynamics by crosslinking mass spectrometry". Current Opinion in Structural Biology. 80 102599. doi: 10.1016/j.sbi.2023.102599 . ISSN   0959-440X. PMID   37104977. S2CID   258351030.
  13. ↑ Barth, Marie; Schmidt, Carla (2021), Marcus, Katrin; Eisenacher, Martin; Sitek, Barbara (eds.), "Quantitative Cross-Linking of Proteins and Protein ComplexesProteinscomplexes", Quantitative Methods in Proteomics, vol. 2228, New York, NY: Springer US, pp. 385–400, doi: 10.1007/978-1-0716-1024-4_26 , ISBN   978-1-0716-1024-4, PMID   33950504, S2CID   233743850
  14. ↑ Fernández-Quintero, Monica L.; Kroell, Katharina B.; Grunewald, Lukas J.; Fischer, Anna-Lena M.; Riccabona, Jakob R.; Liedl, Klaus R. (2022). "CDR loop interactions can determine heavy and light chain pairing preferences in bispecific antibodies". mAbs. 14 (1): 2024118. doi:10.1080/19420862.2021.2024118. ISSN   1942-0870. PMC   8803122 . PMID   35090383.
  15. ↑ Lenz, Swantje; Sinn, Ludwig R.; O’Reilly, Francis J.; Fischer, Lutz; Wegner, Fritz; Rappsilber, Juri (2021-06-11). "Reliable identification of protein-protein interactions by crosslinking mass spectrometry". Nature Communications. 12 (1): 3564. Bibcode:2021NatCo..12.3564L. doi:10.1038/s41467-021-23666-z. ISSN   2041-1723. PMC   8196013 . PMID   34117231.
  16. ↑ DeCaprio, James; Kohl, Thomas O. (2019-02-01). "Cross-Linking Antibodies to Beads with Disuccinimidyl Suberate (DSS)". Cold Spring Harbor Protocols. 2019 (2): pdb.prot098632. doi:10.1101/pdb.prot098632. ISSN   1559-6095. PMID   30710026. S2CID   73441959.
  17. ↑ "Alkenes". Angelo State University . Archived from the original on 2022-12-31. Retrieved 2022-12-31.
  18. ↑ Owais, A.; Khaled, M.; Yilbas, B. S. (2017-01-01), Hashmi, MSJ (ed.), "3.9 Hydrophobicity and Surface Finish", Comprehensive Materials Finishing, Oxford: Elsevier, pp. 137–148, ISBN   978-0-12-803249-7 , retrieved 2022-12-31
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