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Strep-tag® vs His-tag

Benefits of Strep-tag® vs His-tag purification

Strep-tag® and His-tag are both widely used tools for affinity purification via a peptide tag. But when it comes to purity and versatility in applications, some differences between both systems are obvious. The infographic below shows not only the time saving way of Strep-tag® protein purification but also the main key features of the Strep-tag® system at a glance.

Comparing protein purification systems: Strep-tag® vs His-tag

Strep-tag® performs better than His-tag in purification of mammalian-expressed proteins

In combination with high density mammalian protein expression, the His-tag system can lead to poor purification results, if conditions are not optimized. In order to achieve pure proteins for downstream applications from the coupling of the His-tag system and high density mammalian systems, further adjustments like dialysis of the supernatant, lower media:resin ratios or the use of strip-resistant nickel resins become necessary. Such adaptions require additional optimization time and effort, however, these challenges can be avoided by using the Strep-tag® system.

The following whitepaper shows the advantages of the Strep-tag® technology in comparison to the His-tag system as well as the excellent connection of the Strep-tag® technology with two high density mammalian expression systems, the Expi293TM and the ExpiCHOTM expression systems.

Whitepaper Download (pdf)

Protein purification under denaturing conditions

The improved binding affinity of Strep-Tactin®XT to Twin-Strep-tag® enables high protein purities under both native and denaturing conditions. Simultaneously, successor Strep-Tactin®XT preserves all benefits of common Strep-Tactin®, e.g. physiological buffer conditions, mild elution and regeneration of the resin for re-use. Besides this outstanding performance the Strep-Tactin®XT:Twin-Strep-tag® system now offers the possibility to efficiently purify proteins under denaturing circumstances: After successful purification, Strep-Tactin®XT ensured purer protein than the NiNTA:His6-tag system for concentrations up to 6 M urea. Read more in the application note below. 

Application note: Strep-tag® vs His-tag under denaturing conditions

Manual: Purification with Strep-Tactin®XT under denaturing conditions

Strep-tag® - One affinity tag for all protein applications

By exploiting the highly specific interaction, Strep-tagged proteins can be isolated in one step from crude cell lysates in unparalleled purity. Because the Strep-tag® elutes under gentle, physiological conditions it is especially suited for generation of functional proteins e.g. enzymatic proteins. The mild (physiological) purification and elution conditions required for Strep-tag® fusion proteins make them suitable for structural and functional investigations, protein-protein interaction studies, ligand-receptor investigations or even separation of living cells for re-culturing processes. The system is suitable for multiple protein classes, e.g. metallo proteins, membrane proteins, fragile protein complexes with multiple subunits and any other protein class.

The near covalent affinity of Twin-Strep-tag®to Strep-Tactin®XT can be used to efficiently immobilize proteins for assay development. This makes the system to a universal platform and superior to all other affinity systems: one tag can be used for expressionpurificationdetection and immobilization.

For detailed information about further commonly used protein purification affinity tags we recommend the Editorial Article from Biocompare.

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See why His-tag fails in some protein applications and learn more about the benefits and drawbacks of the two systems.


IBA is the original manufacturer of the Strep-tag® system and provides a complete portfolio around protein purification using this affinity system!

High affinity meets high capacity:

Strep-Tactin®XT high capacity

All you need for protein purification and Western Blot detection:

Strep-Tactin®XT Starter Kit

Magnetic Strep-tag® purification at its best!

MagStrep "type3" XT beads