Crosslinkers contain reactive ends to specific functional groups, such as primary amines and sulfhydryls on proteins and antibodies, enabling the covalent joining of or two or more biomolecules. Homobifunctional crosslinkers have the same reactive chemistry at both ends and heterobifunctional have different chemistries at each end. PEGylated crosslinkers have enhanced solubility, increased stability, reduced aggregation, and reduced immunogenicity. Use our crosslinker selection tool to find the optimal reagent for your protein function or interaction application, or access our helpful Bioconjugation Technical Handbook to help improve your crosslinking results.
Learn more about crosslinking chemistries
Learn more about unreactive crosslinker and small molecule removal
Choose the right crosslinker based on reactive chemistry
Amine-to-amine
| Reactive group | Order products | Spacer Arm (Å) | Cleavable? | Water-soluble? | Membrane-permeable? | Reversible? |
|---|---|---|---|---|---|---|
| NHS ester | DSG | 7.7 | N/A | No | Yes | No |
| DSS | 11.4 | N/A | No | Yes | No | |
| BS3 | 11.4 | N/A | Yes | No | No | |
| TSAT (trifunctional) | 4.2 | N/A | No | No | No | |
| BS(PEG)5 | 21.7 | N/A | Yes | No | No | |
| BS(PEG)9 | 35.8 | N/A | Yes | No | No | |
| DSP | 12.0 | Thiols | No | Yes | No | |
| DTSSP | 12.0 | Thiols | Yes | No | No | |
| DST | 6.4 | Periodate | Yes | Yes | No | |
| BSOCOES | 13.0 | Base | No | Yes | No | |
| EGS | 16.1 | Hydoxylamine | No | Yes | Yes | |
| Sulfo-EGS | 16.1 | Hydoxylamine | Yes | No | Yes | |
| Imidoester | DMA | 8.6 | N/A | Yes | Yes | Yes |
| DMP | 9.2 | N/A | Yes | Yes | Yes | |
| DMS | 11.0 | N/A | Yes | Yes | Yes | |
| DTBP | 11.9 | Thiol | Yes | Yes | No | |
| Difluoro | DFDNB | 3.0 | N/A | No | Yes | Yes |
Sulfhydryl-to-sulfhydryl
| Sulfhydryl -to-Sulfhydryl Crosslinkers | Order product | Spacer Arm (Å) | Cleavable? | Water-soluble? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS-Haloacetyl Crosslinkers | SIA | 1.5 | N/A | No | Yes |
| SBAP | 6.2 | N/A | No | Yes | |
| SIAB | 10.6 | N/A | No | Yes | |
| Sulfo-SIAB | 10.6 | N/A | Yes | No | |
| NHS-Maleimide | AMAS | 4.4 | N/A | No | Yes |
| BMPS | 5.9 | N/A | No | Yes | |
| GMBS | 7.3 | N/A | No | Yes | |
| Sulfo-GMBS | 7.3 | N/A | Yes | No | |
| MBS | 7.3 | N/A | No | Yes | |
| Sulfo-MBS | 7.3 | N/A | Yes | No | |
| SMCC | 8.3 | N/A | No | Yes | |
| Sulfo-SMCC | 8.3 | N/A | Yes | No | |
| EMCS | 9.4 | N/A | No | Yes | |
| Sulfo-EMCS | 9.4 | N/A | Yes | No | |
| SMPB | 11.6 | N/A | No | Yes | |
| Sulfo-SMPB | 11.6 | N/A | Yes | No | |
| SMPH | 14.2 | N/A | No | Yes | |
| LC-SMCC | 16.2 | N/A | No | Yes | |
| Sulfo-KMUS | 16.3 | N/A | No | Yes | |
| NHS-Pyridyldithiol Crosslinkers | SPDP | 6.8 | Thiol | No | Yes |
| LC-SPDP | 15.7 | Thiol | No | Yes | |
| Sulfo-LC-SPDP | 15.7 | Thiol | Yes | No | |
| SMPT | 11.2 | Thiol | No | Yes | |
| PEG4-SPDP | 25.7 | Thiol | Yes | No | |
| PEG12-SPDP | 54.1 | Thiol | Yes | No |
Amine-to-sulfhydryl
| Reactive group | Order product | Spacer Arm (Å) | Cleavable? | Water-soluble? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS-Haloacetyl | SIA | 1.5 | N/A | No | Yes |
| SBAP | 6.2 | N/A | No | Yes | |
| SIAB | 10.6 | N/A | No | Yes | |
| Sulfo-SIAB | 10.6 | N/A | Yes | No | |
| NHS-Maleimide | AMAS | 4.4 | N/A | No | Yes |
| BMPS | 5.9 | N/A | No | Yes | |
| GMBS | 7.3 | N/A | No | Yes | |
| Sulfo-GMBS | 7.3 | N/A | Yes | No | |
| MBS | 7.3 | N/A | No | Yes | |
| Sulfo-MBS | 7.3 | N/A | Yes | No | |
| SMCC | 8.3 | N/A | No | Yes | |
| Sulfo-SMCC | 8.3 | N/A | Yes | No | |
| EMCS | 9.4 | N/A | No | Yes | |
| Sulfo-EMCS | 9.4 | N/A | Yes | No | |
| SMPB | 11.6 | N/A | No | Yes | |
| Sulfo-SMPB | 11.6 | N/A | Yes | No | |
| SMPH | 14.2 | N/A | No | Yes | |
| LC-SMCC | 16.2 | N/A | No | Yes | |
| Sulfo-KMUS | 16.3 | N/A | No | Yes | |
| NHS-Pyridyldithiol Crosslinkers | SPDP | 6.8 | Thiol | No | Yes |
| LC-SPDP | 15.7 | Thiol | No | Yes | |
| Sulfo-LC-SPDP | 15.7 | Thiol | Yes | No | |
| SMPT | 11.2 | Thiol | No | Yes | |
| PEG4-SPDP | 25.7 | Thiol | Yes | No | |
| PEG12-SPDP | 54.1 | Thiol | Yes | No |
Carboxyl-to-amine
Sulfhydryl-to-carboxyl
Photoreactive
| Reactive group | Order product | Spacer Arm (Å) | Cleavable by? | Water-soluble ? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS ester/ aryl azide | ANB-NOS | 7.7 Short | No | No | No |
| Sulfo-SANPAH | 18.2 Long | No | Yes | No | |
| NHS ester/ diazirine | SDA | 3.9 Short | No | No | Yes |
| Sulfo-SDA | 3.9 Short | No | Yes | No | |
| LC-SDA | 12.5 Mid | No | No | Yes | |
| Sulfo-LC-SDA | 12.5 Mid | No | Yes | No | |
| SDAD | 13.5 Mid | Thiols | No | Yes | |
| Sulfo-SDAD | 13.5 Mid | Thiols | Yes | No |
Chemoselective
| Reactive group | Order product | Spacer Arm (Å) | Cleavable by? | Water-soluble ? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS ester/ aryl azide | NHS-Azide | 2.5 | No | No | ND* |
| NHS-PEG4-Azide | 18.9 | No | No | ND* | |
| NHS ester/ diazirine | NHS-Phosphine | 5.4 | No | No | ND* |
* Not determined
Amine-to-amine
| Reactive group | Order products | Spacer Arm (Å) | Cleavable? | Water-soluble? | Membrane-permeable? | Reversible? |
|---|---|---|---|---|---|---|
| NHS ester | DSG | 7.7 | N/A | No | Yes | No |
| DSS | 11.4 | N/A | No | Yes | No | |
| BS3 | 11.4 | N/A | Yes | No | No | |
| TSAT (trifunctional) | 4.2 | N/A | No | No | No | |
| BS(PEG)5 | 21.7 | N/A | Yes | No | No | |
| BS(PEG)9 | 35.8 | N/A | Yes | No | No | |
| DSP | 12.0 | Thiols | No | Yes | No | |
| DTSSP | 12.0 | Thiols | Yes | No | No | |
| DST | 6.4 | Periodate | Yes | Yes | No | |
| BSOCOES | 13.0 | Base | No | Yes | No | |
| EGS | 16.1 | Hydoxylamine | No | Yes | Yes | |
| Sulfo-EGS | 16.1 | Hydoxylamine | Yes | No | Yes | |
| Imidoester | DMA | 8.6 | N/A | Yes | Yes | Yes |
| DMP | 9.2 | N/A | Yes | Yes | Yes | |
| DMS | 11.0 | N/A | Yes | Yes | Yes | |
| DTBP | 11.9 | Thiol | Yes | Yes | No | |
| Difluoro | DFDNB | 3.0 | N/A | No | Yes | Yes |
Sulfhydryl-to-sulfhydryl
| Sulfhydryl -to-Sulfhydryl Crosslinkers | Order product | Spacer Arm (Å) | Cleavable? | Water-soluble? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS-Haloacetyl Crosslinkers | SIA | 1.5 | N/A | No | Yes |
| SBAP | 6.2 | N/A | No | Yes | |
| SIAB | 10.6 | N/A | No | Yes | |
| Sulfo-SIAB | 10.6 | N/A | Yes | No | |
| NHS-Maleimide | AMAS | 4.4 | N/A | No | Yes |
| BMPS | 5.9 | N/A | No | Yes | |
| GMBS | 7.3 | N/A | No | Yes | |
| Sulfo-GMBS | 7.3 | N/A | Yes | No | |
| MBS | 7.3 | N/A | No | Yes | |
| Sulfo-MBS | 7.3 | N/A | Yes | No | |
| SMCC | 8.3 | N/A | No | Yes | |
| Sulfo-SMCC | 8.3 | N/A | Yes | No | |
| EMCS | 9.4 | N/A | No | Yes | |
| Sulfo-EMCS | 9.4 | N/A | Yes | No | |
| SMPB | 11.6 | N/A | No | Yes | |
| Sulfo-SMPB | 11.6 | N/A | Yes | No | |
| SMPH | 14.2 | N/A | No | Yes | |
| LC-SMCC | 16.2 | N/A | No | Yes | |
| Sulfo-KMUS | 16.3 | N/A | No | Yes | |
| NHS-Pyridyldithiol Crosslinkers | SPDP | 6.8 | Thiol | No | Yes |
| LC-SPDP | 15.7 | Thiol | No | Yes | |
| Sulfo-LC-SPDP | 15.7 | Thiol | Yes | No | |
| SMPT | 11.2 | Thiol | No | Yes | |
| PEG4-SPDP | 25.7 | Thiol | Yes | No | |
| PEG12-SPDP | 54.1 | Thiol | Yes | No |
Amine-to-sulfhydryl
| Reactive group | Order product | Spacer Arm (Å) | Cleavable? | Water-soluble? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS-Haloacetyl | SIA | 1.5 | N/A | No | Yes |
| SBAP | 6.2 | N/A | No | Yes | |
| SIAB | 10.6 | N/A | No | Yes | |
| Sulfo-SIAB | 10.6 | N/A | Yes | No | |
| NHS-Maleimide | AMAS | 4.4 | N/A | No | Yes |
| BMPS | 5.9 | N/A | No | Yes | |
| GMBS | 7.3 | N/A | No | Yes | |
| Sulfo-GMBS | 7.3 | N/A | Yes | No | |
| MBS | 7.3 | N/A | No | Yes | |
| Sulfo-MBS | 7.3 | N/A | Yes | No | |
| SMCC | 8.3 | N/A | No | Yes | |
| Sulfo-SMCC | 8.3 | N/A | Yes | No | |
| EMCS | 9.4 | N/A | No | Yes | |
| Sulfo-EMCS | 9.4 | N/A | Yes | No | |
| SMPB | 11.6 | N/A | No | Yes | |
| Sulfo-SMPB | 11.6 | N/A | Yes | No | |
| SMPH | 14.2 | N/A | No | Yes | |
| LC-SMCC | 16.2 | N/A | No | Yes | |
| Sulfo-KMUS | 16.3 | N/A | No | Yes | |
| NHS-Pyridyldithiol Crosslinkers | SPDP | 6.8 | Thiol | No | Yes |
| LC-SPDP | 15.7 | Thiol | No | Yes | |
| Sulfo-LC-SPDP | 15.7 | Thiol | Yes | No | |
| SMPT | 11.2 | Thiol | No | Yes | |
| PEG4-SPDP | 25.7 | Thiol | Yes | No | |
| PEG12-SPDP | 54.1 | Thiol | Yes | No |
Carboxyl-to-amine
Sulfhydryl-to-carboxyl
Photoreactive
| Reactive group | Order product | Spacer Arm (Å) | Cleavable by? | Water-soluble ? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS ester/ aryl azide | ANB-NOS | 7.7 Short | No | No | No |
| Sulfo-SANPAH | 18.2 Long | No | Yes | No | |
| NHS ester/ diazirine | SDA | 3.9 Short | No | No | Yes |
| Sulfo-SDA | 3.9 Short | No | Yes | No | |
| LC-SDA | 12.5 Mid | No | No | Yes | |
| Sulfo-LC-SDA | 12.5 Mid | No | Yes | No | |
| SDAD | 13.5 Mid | Thiols | No | Yes | |
| Sulfo-SDAD | 13.5 Mid | Thiols | Yes | No |
Chemoselective
| Reactive group | Order product | Spacer Arm (Å) | Cleavable by? | Water-soluble ? | Membrane permeable? |
|---|---|---|---|---|---|
| NHS ester/ aryl azide | NHS-Azide | 2.5 | No | No | ND* |
| NHS-PEG4-Azide | 18.9 | No | No | ND* | |
| NHS ester/ diazirine | NHS-Phosphine | 5.4 | No | No | ND* |
* Not determined
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