Cyclic peptides as proteases

A reevaluation

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Abstract

A recent report [Atassi, M. Z. and Manshouri, T.(1993) Proc. Natl. Acad. Sci. USA 90, 8282-8286] described the design and synthesis of two 29-amino acid cyclic peptides that were reported to hydrolyze both ester and amide bonds with chymotrypsin-like or trypsin-like specificity. We have synthesized the trypsin-mimic peptide (TrPepz) and detect no activity toward either ester or peptide substrates. The same result was independently obtained by Wells et al. [Wells, J. A., Fairbrother, W. J., Otlewski, J., Laskowski, M., Jr., and Burnier, J. (1994) Proc. Natl. Acad. Sci. USA 91, 4110-4114.] Additionally, we found that Atassi and Manshouri failed to obtain accurate kinetic constants for trypsin- and chymotrypsin-catalyzed ester hydrolysis because the high concentrations of trypsin and chymotrypsin that they report using would have prevented evaluation of initial rates. These findings are incompatible with the claims, reported by Atassi and Manshouri, that TrPepz has trypsin-like activity.

Original languageEnglish (US)
Pages (from-to)4106-4109
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number10
StatePublished - May 10 1994

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Cyclic Peptides
Trypsin
Esters
Peptide Hydrolases
Peptides
Chymotrypsin
Amides
Hydrolysis
Amino Acids
TrPepz
trypsin drug combination chymotrypsin

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Cyclic peptides as proteases: A reevaluation",
abstract = "A recent report [Atassi, M. Z. and Manshouri, T.(1993) Proc. Natl. Acad. Sci. USA 90, 8282-8286] described the design and synthesis of two 29-amino acid cyclic peptides that were reported to hydrolyze both ester and amide bonds with chymotrypsin-like or trypsin-like specificity. We have synthesized the trypsin-mimic peptide (TrPepz) and detect no activity toward either ester or peptide substrates. The same result was independently obtained by Wells et al. [Wells, J. A., Fairbrother, W. J., Otlewski, J., Laskowski, M., Jr., and Burnier, J. (1994) Proc. Natl. Acad. Sci. USA 91, 4110-4114.] Additionally, we found that Atassi and Manshouri failed to obtain accurate kinetic constants for trypsin- and chymotrypsin-catalyzed ester hydrolysis because the high concentrations of trypsin and chymotrypsin that they report using would have prevented evaluation of initial rates. These findings are incompatible with the claims, reported by Atassi and Manshouri, that TrPepz has trypsin-like activity.",
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AU - Phillips, Margaret A.

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