Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme

Alex L. Harris; Jill S. Gregory; Alan L. Maycock; Todd L. Graybill; I. Kelly Osifo; Stanley J. Schmidt; Roland E. Dolle

doi:10.1016/0960-894X(95)00042-R

Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme

Alex L. Harris, Jill S. Gregory, Alan L. Maycock, Todd L. Graybill, I. Kelly Osifo, Stanley J. Schmidt, Roland E. Dolle

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Z-Leu-Arg-(7-methoxynaphthyl)amide (1) is a substrate for calpain I. The specificity constant for 1 ( k_cat K_m = 1405 ± 40 M^-1s^-1) is 10x greater than for any previously reported fluorogenic substrate. Using this substrate, a sensitive, continuous fluorogenic assay was developed permitting the identification of Z-(D)Ala-Leu-Phe-(OCO-2,6-Fl₂-Ph) (69) as the first selective (>100-fold versus cathepsins B and L) time-dependent inhibitor of the enzyme.

Original language	English
Pages (from-to)	393-398
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	5
Issue number	4
DOIs	https://doi.org/10.1016/0960-894X(95)00042-R
State	Published - Feb 16 1995

Access to Document

10.1016/0960-894X(95)00042-R

Cite this

Harris, A. L., Gregory, J. S., Maycock, A. L., Graybill, T. L., Osifo, I. K., Schmidt, S. J., & Dolle, R. E. (1995). Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme. Bioorganic and Medicinal Chemistry Letters, 5(4), 393-398. https://doi.org/10.1016/0960-894X(95)00042-R

@article{fdc1f47857b64c2bb9bfa2a50872e4c8,

title = "Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme",

abstract = "Z-Leu-Arg-(7-methoxynaphthyl)amide (1) is a substrate for calpain I. The specificity constant for 1 ( kcat Km = 1405 ± 40 M-1s-1) is 10x greater than for any previously reported fluorogenic substrate. Using this substrate, a sensitive, continuous fluorogenic assay was developed permitting the identification of Z-(D)Ala-Leu-Phe-(OCO-2,6-Fl2-Ph) (69) as the first selective (>100-fold versus cathepsins B and L) time-dependent inhibitor of the enzyme.",

author = "Harris, {Alex L.} and Gregory, {Jill S.} and Maycock, {Alan L.} and Graybill, {Todd L.} and Osifo, {I. Kelly} and Schmidt, {Stanley J.} and Dolle, {Roland E.}",

year = "1995",

month = feb,

day = "16",

doi = "10.1016/0960-894X(95)00042-R",

language = "English",

volume = "5",

pages = "393--398",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

number = "4",

}

Harris, AL, Gregory, JS, Maycock, AL, Graybill, TL, Osifo, IK, Schmidt, SJ & Dolle, RE 1995, 'Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme', Bioorganic and Medicinal Chemistry Letters, vol. 5, no. 4, pp. 393-398. https://doi.org/10.1016/0960-894X(95)00042-R

Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme. / Harris, Alex L.; Gregory, Jill S.; Maycock, Alan L. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 5, No. 4, 16.02.1995, p. 393-398.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme

AU - Harris, Alex L.

AU - Gregory, Jill S.

AU - Maycock, Alan L.

AU - Graybill, Todd L.

AU - Osifo, I. Kelly

AU - Schmidt, Stanley J.

AU - Dolle, Roland E.

PY - 1995/2/16

Y1 - 1995/2/16

N2 - Z-Leu-Arg-(7-methoxynaphthyl)amide (1) is a substrate for calpain I. The specificity constant for 1 ( kcat Km = 1405 ± 40 M-1s-1) is 10x greater than for any previously reported fluorogenic substrate. Using this substrate, a sensitive, continuous fluorogenic assay was developed permitting the identification of Z-(D)Ala-Leu-Phe-(OCO-2,6-Fl2-Ph) (69) as the first selective (>100-fold versus cathepsins B and L) time-dependent inhibitor of the enzyme.

AB - Z-Leu-Arg-(7-methoxynaphthyl)amide (1) is a substrate for calpain I. The specificity constant for 1 ( kcat Km = 1405 ± 40 M-1s-1) is 10x greater than for any previously reported fluorogenic substrate. Using this substrate, a sensitive, continuous fluorogenic assay was developed permitting the identification of Z-(D)Ala-Leu-Phe-(OCO-2,6-Fl2-Ph) (69) as the first selective (>100-fold versus cathepsins B and L) time-dependent inhibitor of the enzyme.

UR - http://www.scopus.com/inward/record.url?scp=0028836877&partnerID=8YFLogxK

U2 - 10.1016/0960-894X(95)00042-R

DO - 10.1016/0960-894X(95)00042-R

M3 - Article

AN - SCOPUS:0028836877

SN - 0960-894X

VL - 5

SP - 393

EP - 398

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme

Abstract

Access to Document

Other files and links

Fingerprint

Cite this