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Crosslinkers at a Glance

Crosslinking is the process of chemically joining two or more molecules by a covalent bond. Crosslinking reagents contain two or more reactive ends that are capable of attaching to specific functional groups (primary amines, sulfhydryls, etc.) on proteins or other molecules.

Only a small number of reactive chemistries are used as the basis for synthesizing the reagents that are most popular for protein conjugation techniques. However, these five or six types of reactive groups can be combined in a variety of ways and attached to molecular backbones of various lengths and chemical properties to create many specific crosslinking reagents.

Choosing among the commercially available options can seem overwhelming until one considers the particular application needs and categorizes reagents by their general features. The following two tables provide a comprehensive list of Thermo Scientific Pierce Crosslinking Reagents classified as succinctly as possible by their most important features.

Page Contents:

Homobifunctional Crosslinkers (both ends the same)
Heterobifunctional Crosslinkers (different reactive ends)

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Overview of Crosslinking

Chemistry of Crosslinking

Crosslinking Applications

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All Crosslinkers

Crosslinker Selection Guide
(Interactive version of this page)

Homobifunctional Crosslinkers (both ends the same)

**Homobifunctional Crosslinkers.** A list of crosslinking reagents that have the same type of reactive group at either end. Reagents are classified by what chemical groups they crosslink (left column) and their chemical composition (middle column). Products are listed in order of increasing length within each table cell.
Crosslinking Target	Reactive Groups, Features	Crosslinker Products
Amine-to-Amine	NHS esters	DSG DSS BS3 TSAT (trifunctional)
	NHS esters, PEG spacer	BS(PEG)5 BS(PEG)9
	NHS esters, thiol-cleavable	DSP DTSSP
	NHS esters, misc-cleavable	DST BSOCOES EGS Sulfo-EGS
	Imidoesters	DMA DMP DMS
	Imidoesters, thiol-cleavable	DTBP
	Other	DFDNB
Sulfhydryl-to-Sulfhydryl	Maleimides	BMOE BMB BMH TMEA (trifunctional)
	Maleimides, PEG spacer	BM(PEG)2 BM(PEG)3
	Maleimides, cleavable	BMDB DTME

Heterobifunctional Crosslinkers (different reactive ends)

**Heterobifunctional Crosslinkers.** A list of crosslinking reagents that have the different reactive groups at either end. Reagents are classified by what chemical groups they crosslink (left column) and their chemical composition (middle column). Products are listed in order of increasing length within each table cell.
Crosslinking Targets	Crosslinker Reactive Groups, Features	Crosslinker Products
Amine-to-Sulfhydryl	NHS ester / Maleimide	AMAS BMPS GMBS and Sulfo-GMBS MBS and Sulfo-MBS SMCC and Sulfo-SMCC EMCS and Sulfo-EMCS SMPB and Sulfo-SMPB SMPH LC-SMCC Sulfo-KMUS
	NHS ester / Maleimide, PEG spacer	SM(PEG)2 SM(PEG)4 SM(PEG)6 SM(PEG)8 SM(PEG)12 SM(PEG)24
	NHS ester / Pyridyldithiol, cleavable	SPDP LC-SPDP and Sulfo-LC-SPDP SMPT PEG4-SPDP PEG12-SPDP
	NHS esters / Haloacetyl	SIA SBAP SIAB Sulfo-SIAB
Amine-to-Nonselective (Photo-reactive)	NHS ester / Aryl Azide	ANB-NOS Sulfo-SANPAH
	NHS ester / Diazirine	SDA and Sulfo-SDA LC-SDA and Sulfo-LC-SDA
	NHS ester / Diazirine, cleavable	SDAD and Sulfo-SDAD
Carboxyl-to-Amine	Carbodiimide	DCC EDC See also: NHS and Sulfo-NHS
Sulfhydryl-to-Carbohydrate	Maleimide / Hydrazide	BMPH EMCH MPBH KMUH
Sulfhydryl-to-Carbohydrate	Pyridyldithiol / Hydrazide	PDPH
Hydroxyl-to-Sulfhydryl	Isocyanate / Maleimide	PMPI
Amine-to-DNA	NHS ester / Psoralen	SPB

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