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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.

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

Pros and Cons of Strep-tag® and His-tag

  Strep-tag® His-tag

+ high purity, even under denaturing conditions and in batch purification
+ no additional purification necessary
+ physiological buffer conditions
+ mild reversibility without changing the overall buffer conditions
+ purification of metallo-proteins
+ beneficial for membrane proteins
+ SPR and other high affinity applications

+ resin can be recharged
+ denaturing conditions with Gua-HCl

Cons - less yield compared to His-tag
- not suitable for metal proteins
- interacts unspecifically with complex forming amino acids
- does not tolerate chelating agents
- works only best for E. coli expression (often problematic after mammalia expression)
- time consuming elution gradient for higher purity


Watch this webinar and learn more about the benefits and drawbacks of the two systems:Strep-tag® vs His-tag

Additional data

The 3rd generation Strep-tag® system can now be used for purification under denaturing conditions using up to 6 M urea. Check the application note for a comparison of Strep-tag® system III to His-tag:NiNTA purification under denaturing conditions.

Download experimental data:

Strep-tag® vs His-tag under denaturing conditions

Download protocol:

Purification with Strep-Tactin®XT under denaturing conditions


For further reading we recommend this Editorial Article from Biocompare.


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