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Engineered Discoidin Domain from Factor VIII Binds αvβ3 Integrin with Antibody-like Affinity


Kym, Eugene Yongshik (Gene) (2014) Engineered Discoidin Domain from Factor VIII Binds αvβ3 Integrin with Antibody-like Affinity. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/PTZH-PB29.


Alternative scaffolds are non-antibody proteins that can be engineered to bind new targets. They have found useful niches in the therapeutic space due to their smaller size and the ease with which they can be engineered to be bispecific. We sought a new scaffold that could be used for therapeutic ends and chose the C2 discoidin domain of factor VIII, which is well studied and of human origin. Using yeast surface display, we engineered the C2 domain to bind to αvβ3 integrin with a 16 nM affinity while retaining its thermal stability and monomeric nature. We obtained a crystal structure of the engineered domain at 2.1 Å resolution. We have christened this discoidin domain alternative scaffold the “discobody.”

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:alternative scaffold, antibody engineering, integrin, discoidin domain, discobody
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Mayo, Stephen L.
Thesis Committee:
  • Deshaies, Raymond Joseph (chair)
  • Chan, David C.
  • Tirrell, David A.
  • Mayo, Stephen L.
Defense Date:23 April 2014
Funding AgencyGrant Number
Defense Advanced Research Projects Agency NSSEFF N00244-09-1-0011, N00244-09-1-0082
Gordon and Betty Moore Foundation GBMF2809
Record Number:CaltechTHESIS:05302014-171245991
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8449
Deposited By: Eugene Kym
Deposited On:03 Jun 2014 19:29
Last Modified:04 Oct 2019 00:05

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