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Protein Prosthesis:  A Nonnatural Residue Accelerates Folding and Increases Stability

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journal contribution
posted on 30.05.2003, 00:00 by Ulrich Arnold, Matthew P. Hinderaker, Jens Köditz, Ralph Golbik, Renate Ulbrich-Hofmann, Ronald T. Raines
Nonnatural residues can endow proteins with desirable properties. Here, replacing a proline residue that has a cis peptide bond in native ribonuclease A with 5,5-dimethyl-l-proline is shown to accelerate protein folding by 6-fold and enhance conformational stability by ΔTm = 2.8 ± 0.3 °C while having no effect on enzymatic activity. The rational use of this and other prosthetic segments could enable chemotherapeutic proteins to survive longer in vivo or retain activity after oral administration.

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