Research ExplorerPublicationsPeptides targeting caspase inhibitors

Peptides targeting caspase inhibitors

Standard

Peptides targeting caspase inhibitors. / Tamm, Ingo; Trepel, Martin; Cardó-Vila, Marina; Sun, Yan V; Welsh, Kate; Cabezas, Edelmira; Swatterthwait, Arnold; Arap, Wadih; Reed, John C; Pasqualini, Renata.

In: J BIOL CHEM, Vol. 278, No. 16, 18.04.2003, p. 14401-5.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Tamm, I, Trepel, M, Cardó-Vila, M, Sun, YV, Welsh, K, Cabezas, E, Swatterthwait, A, Arap, W, Reed, JC & Pasqualini, R 2003, 'Peptides targeting caspase inhibitors', J BIOL CHEM, vol. 278, no. 16, pp. 14401-5. https://doi.org/10.1074/jbc.M210133200

APA

Tamm, I., Trepel, M., Cardó-Vila, M., Sun, Y. V., Welsh, K., Cabezas, E., Swatterthwait, A., Arap, W., Reed, J. C., & Pasqualini, R. (2003). Peptides targeting caspase inhibitors. J BIOL CHEM, 278(16), 14401-5. https://doi.org/10.1074/jbc.M210133200

Vancouver

Tamm I, Trepel M, Cardó-Vila M, Sun YV, Welsh K, Cabezas E et al. Peptides targeting caspase inhibitors. J BIOL CHEM. 2003 Apr 18;278(16):14401-5. https://doi.org/10.1074/jbc.M210133200

Bibtex

@article{7f144cc851a14259a3dfab8c2124b4d4,
title = "Peptides targeting caspase inhibitors",
abstract = "Here we report on the identification of peptides targeting the X-inhibitor of apoptosis protein (XIAP). XIAP functions as a caspase inhibitor and is a member of the inhibitors of apoptosis (IAP) family of proteins. IAPs are often overexpressed in cancers and leukemias and are associated with an unfavorable clinical prognosis. We have selected peptides from a phage library by using recombinant full-length human XIAP or a fragment containing only the baculovirus IAP repeat 2 (BIR2) domain. A consensus motif, C(D/E/P)(W/F/Y)-acid/basic-XC, was recovered from two independent screenings by using different libraries. Phage-displaying variations of the consensus sequence bound specifically to the BIR2 domain of XIAP but not to other IAPs. The interaction was specific as it could be blocked by the cognate synthetic peptides in a dose-dependent manner. Phage displaying the XIAP-binding motif CEFESC bound to the BIR2 domain of XIAP with an estimated dissociation constant of 1.8 nm as determined by surface plasmon resonance. Protein-protein interaction assays revealed that caspase-3 and caspase-7 (but not caspase-8) blocked the binding of the CEFESC phage to XIAP, indicating that this peptide targets a domain within XIAP that is related to the caspase-binding site. In fact, the sequence EFES is homologous to a loop unique to the executioner caspase-3 and caspase-7 that are targeted by XIAP. Finally, we demonstrated that an internalizing version of the XIAP-binding peptide identified in our screenings (PFKQ) can induce programmed cell death in leukemia cells. Peptides interacting with XIAP could serve as prototypes for the design of low molecular weight modulators of apoptosis.",
keywords = "Amino Acid Motifs, Apoptosis, Binding Sites, Caspase 3, Caspase 7, Caspase 8, Caspase 9, Caspase Inhibitors, Caspases, Cell Survival, Dose-Response Relationship, Drug, Enzyme Inhibitors, Humans, Ligands, Peptide Biosynthesis, Peptide Library, Peptides, Protein Binding, Protein Structure, Tertiary, Proteins, Surface Plasmon Resonance, Time Factors, X-Linked Inhibitor of Apoptosis Protein, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.",
author = "Ingo Tamm and Martin Trepel and Marina Card{\'o}-Vila and Sun, {Yan V} and Kate Welsh and Edelmira Cabezas and Arnold Swatterthwait and Wadih Arap and Reed, {John C} and Renata Pasqualini",
year = "2003",
month = apr,
day = "18",
doi = "10.1074/jbc.M210133200",
language = "English",
volume = "278",
pages = "14401--5",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "16",

}

RIS

TY - JOUR

T1 - Peptides targeting caspase inhibitors

AU - Tamm, Ingo

AU - Trepel, Martin

AU - Cardó-Vila, Marina

AU - Sun, Yan V

AU - Welsh, Kate

AU - Cabezas, Edelmira

AU - Swatterthwait, Arnold

AU - Arap, Wadih

AU - Reed, John C

AU - Pasqualini, Renata

PY - 2003/4/18

Y1 - 2003/4/18

N2 - Here we report on the identification of peptides targeting the X-inhibitor of apoptosis protein (XIAP). XIAP functions as a caspase inhibitor and is a member of the inhibitors of apoptosis (IAP) family of proteins. IAPs are often overexpressed in cancers and leukemias and are associated with an unfavorable clinical prognosis. We have selected peptides from a phage library by using recombinant full-length human XIAP or a fragment containing only the baculovirus IAP repeat 2 (BIR2) domain. A consensus motif, C(D/E/P)(W/F/Y)-acid/basic-XC, was recovered from two independent screenings by using different libraries. Phage-displaying variations of the consensus sequence bound specifically to the BIR2 domain of XIAP but not to other IAPs. The interaction was specific as it could be blocked by the cognate synthetic peptides in a dose-dependent manner. Phage displaying the XIAP-binding motif CEFESC bound to the BIR2 domain of XIAP with an estimated dissociation constant of 1.8 nm as determined by surface plasmon resonance. Protein-protein interaction assays revealed that caspase-3 and caspase-7 (but not caspase-8) blocked the binding of the CEFESC phage to XIAP, indicating that this peptide targets a domain within XIAP that is related to the caspase-binding site. In fact, the sequence EFES is homologous to a loop unique to the executioner caspase-3 and caspase-7 that are targeted by XIAP. Finally, we demonstrated that an internalizing version of the XIAP-binding peptide identified in our screenings (PFKQ) can induce programmed cell death in leukemia cells. Peptides interacting with XIAP could serve as prototypes for the design of low molecular weight modulators of apoptosis.

AB - Here we report on the identification of peptides targeting the X-inhibitor of apoptosis protein (XIAP). XIAP functions as a caspase inhibitor and is a member of the inhibitors of apoptosis (IAP) family of proteins. IAPs are often overexpressed in cancers and leukemias and are associated with an unfavorable clinical prognosis. We have selected peptides from a phage library by using recombinant full-length human XIAP or a fragment containing only the baculovirus IAP repeat 2 (BIR2) domain. A consensus motif, C(D/E/P)(W/F/Y)-acid/basic-XC, was recovered from two independent screenings by using different libraries. Phage-displaying variations of the consensus sequence bound specifically to the BIR2 domain of XIAP but not to other IAPs. The interaction was specific as it could be blocked by the cognate synthetic peptides in a dose-dependent manner. Phage displaying the XIAP-binding motif CEFESC bound to the BIR2 domain of XIAP with an estimated dissociation constant of 1.8 nm as determined by surface plasmon resonance. Protein-protein interaction assays revealed that caspase-3 and caspase-7 (but not caspase-8) blocked the binding of the CEFESC phage to XIAP, indicating that this peptide targets a domain within XIAP that is related to the caspase-binding site. In fact, the sequence EFES is homologous to a loop unique to the executioner caspase-3 and caspase-7 that are targeted by XIAP. Finally, we demonstrated that an internalizing version of the XIAP-binding peptide identified in our screenings (PFKQ) can induce programmed cell death in leukemia cells. Peptides interacting with XIAP could serve as prototypes for the design of low molecular weight modulators of apoptosis.

KW - Amino Acid Motifs

KW - Apoptosis

KW - Binding Sites

KW - Caspase 3

KW - Caspase 7

KW - Caspase 8

KW - Caspase 9

KW - Caspase Inhibitors

KW - Caspases

KW - Cell Survival

KW - Dose-Response Relationship, Drug

KW - Enzyme Inhibitors

KW - Humans

KW - Ligands

KW - Peptide Biosynthesis

KW - Peptide Library

KW - Peptides

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Proteins

KW - Surface Plasmon Resonance

KW - Time Factors

KW - X-Linked Inhibitor of Apoptosis Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1074/jbc.M210133200

DO - 10.1074/jbc.M210133200

M3 - SCORING: Journal article

C2 - 12538646

VL - 278

SP - 14401

EP - 14405

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 16

ER -