DOI: 10.1111/j.1399-3011.1994.tb00573.x. Preparation and evaluation of peptidic aspartyl hemiacetals as reversible inhibitors of interleukin‐l β converting enzyme (ICE)

Preparation and evaluation of peptidic aspartyl hemiacetals as reversible inhibitors of interleukin‐l β converting enzyme (ICE)

10.1111/j.1399-3011.1994.tb00573.x

Crossref journal-article

Wiley

International Journal of Peptide and Protein Research (311)

Abstract

Aspartyl aldehyde, Ac‐Tyr‐Val‐Ala‐Asp‐H 1 (L–709,049), has been reported to be a potent, reversible inhibitor of interleukin‐1β converting enzyme (ICE) [Thornberry, N.A. et al. (1992) Nature (London)356, 768–774], In the context of our own work, we have developed a general synthetic approach to peptidic aspartyl aldehydes. Semicarbazone derivative, H‐Asp(Ot‐Bu)‐Sc 4, was identified as a stable, masked aspartyl aldehyde equivalent. We have used 4 to synthesize a series of mono‐, di‐ and tripeptide aldehydes, and multigram quantities of Ac‐Tyr‐Val‐Ala‐Asp‐H 1, Ac‐Tyr‐Val‐Lys‐Asp‐Sc 21 and Ac‐Tyr‐Val‐Lys‐Asp‐H 2. Biological evaluation of these aspartyl aldehydes and derivatives suggests that the tripeptide scaffold, Z‐Val‐Ala‐Asp, is a peptide scaffold that retains good potency and selectivity for ICE.

Bibliography

GRAYBILL, T. L., DOLLE, R. E., HELASZEK, C. T., MILLER, R. E., & ATOR, M. A. (1994). Preparation and evaluation of peptidic aspartyl hemiacetals as reversible inhibitors of interleukinâl Î² converting enzyme (ICE). International Journal of Peptide and Protein Research, 44(2), 173â182. Portico.

Authors 5

TODD L. GRAYBILL (first)
ROLAND E. DOLLE (additional)
CARLA T. HELASZEK (additional)
ROBERT E. MILLER (additional)
MARK A. ATOR (additional)

References 24 Referenced 53

10.1056/NEJM199301143280207
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Dates

Type	When
Created	15 years ago (Aug. 9, 2010, 7:59 p.m.)
Deposited	1 year, 10 months ago (Oct. 24, 2023, 2:29 a.m.)
Indexed	1 month, 2 weeks ago (July 16, 2025, 8:24 a.m.)
Issued	31 years, 1 month ago (Aug. 1, 1994)
Published	31 years, 1 month ago (Aug. 1, 1994)
Published Online	16 years, 7 months ago (Jan. 12, 2009)
Published Print	31 years, 1 month ago (Aug. 1, 1994)

Funders 0

None

BibTeX

@article{GRAYBILL_1994, title={Preparation and evaluation of peptidic aspartyl hemiacetals as reversible inhibitors of interleukin‐l β converting enzyme (ICE)}, volume={44}, ISSN={0367-8377}, url={http://dx.doi.org/10.1111/j.1399-3011.1994.tb00573.x}, DOI={10.1111/j.1399-3011.1994.tb00573.x}, number={2}, journal={International Journal of Peptide and Protein Research}, publisher={Wiley}, author={GRAYBILL, TODD L. and DOLLE, ROLAND E. and HELASZEK, CARLA T. and MILLER, ROBERT E. and ATOR, MARK A.}, year={1994}, month=aug, pages={173–182} }

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