Altering the Tat-derived peptide bioactivity landscape by changing the arginine side chain length

Cheng Hsun Wu, Yi Ping Chen, Chung Yuan Mou, Richard P. Cheng

Research output: Contribution to journalArticle

11 Citations (Scopus)


Mutations of proteins with dual activities that lead to enhancement of one activity are frequently accompanied by attenuation of the other activity. However, this mutational negative trade-off phenomenon typically only involves the canonical 20 amino acids. To test the effect of non-canonical amino acids on the negative trade-off phenomenon, two bioactivities of HIV-1 Tat-derived peptides were monitored upon changing the Arg side chain length. In contrast to the expected mutational negative trade-off, shortening Arg by one methylene resulted in both higher TAR RNA binding specificity and higher cellular uptake. These results suggest that introducing previously unexploited building blocks, even if the difference is only one methylene, can alter the peptide bioactivity landscape leading to the enhancement of multiple bioactivities.

Original languageEnglish
Pages (from-to)473-480
Number of pages8
JournalAmino Acids
Issue number2
Publication statusPublished - Feb 2013
Externally publishedYes



  • Arginine
  • Cellular uptake
  • RNA recognition
  • Side chain length

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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