Designing Cytokine Variants by Phage-Display

Heidi      Schooltink; Stefan      Rose-John

doi:10.2174/1386207053258550

Abstract

Cytokines are important mediators of many cellular functions including coordination of the immune system and regulation of regenerative processes. Therefore, cytokines can be exploited for therapeutic strategies. Cytokines can be altered in a way that their biologic activity is enhanced or antagonized. This can be accomplished by changing the interaction of cytokines with their cognate cytokine receptor complexes. Therefore, many research groups tried to design cytokines, which bind with higher affinity to their receptors. Alternatively, cytokine variants have been created which do bind to their receptors but do not elicit a signal. Such strategies have been followed using high throughput techniques like error-prone polymerase chain reaction and phage display. Designer cytokines can be used to specifically inhibit cytokine functions. Moreover, peptides have been generated with the help of phage display techniques, which exhibit cytokine activity. Surprisingly, such mimetic peptides do not show any sequence similarity to the parental cytokines. Such peptide mimetics can be used as lead structures for the generation of non-peptidic chemical compounds with cytokine activity.

Keywords: affinity, cytokine, cytokine antagonist, cytokine receptor, designer cytokine, error-prone pcr, phage display

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