Direct targeting of Rab-GTPase-effector interactions

Jochen Spiegel; Philipp M Cromm; Aymelt Itzen; Roger S Goody; Tom N Grossmann; Herbert Waldmann

doi:10.1002/anie.201308568

Direct targeting of Rab-GTPase-effector interactions

Standard

Direct targeting of Rab-GTPase-effector interactions. / Spiegel, Jochen; Cromm, Philipp M; Itzen, Aymelt; Goody, Roger S; Grossmann, Tom N; Waldmann, Herbert.

In: ANGEW CHEM INT EDIT, Vol. 53, No. 9, 24.02.2014, p. 2498-503.

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

Harvard

Spiegel, J, Cromm, PM, Itzen, A, Goody, RS, Grossmann, TN & Waldmann, H 2014, 'Direct targeting of Rab-GTPase-effector interactions', ANGEW CHEM INT EDIT, vol. 53, no. 9, pp. 2498-503. https://doi.org/10.1002/anie.201308568

APA

Spiegel, J., Cromm, P. M., Itzen, A., Goody, R. S., Grossmann, T. N., & Waldmann, H. (2014). Direct targeting of Rab-GTPase-effector interactions. ANGEW CHEM INT EDIT, 53(9), 2498-503. https://doi.org/10.1002/anie.201308568

Vancouver

Spiegel J, Cromm PM, Itzen A, Goody RS, Grossmann TN, Waldmann H. Direct targeting of Rab-GTPase-effector interactions. ANGEW CHEM INT EDIT. 2014 Feb 24;53(9):2498-503. https://doi.org/10.1002/anie.201308568

Bibtex

@article{2e147be0586648038b0c20c8384de804,

title = "Direct targeting of Rab-GTPase-effector interactions",

abstract = "Small GTPases are molecular switches using GDP/GTP alternation to control numerous vital cellular processes. Although aberrant function and regulation of GTPases are implicated in various human diseases, direct targeting of this class of proteins has proven difficult, as GTPase signaling and regulation is mediated by extensive and shallow protein interfaces. Here we report the development of inhibitors of protein-protein interactions involving Rab proteins, a subfamily of GTPases, which are key regulators of vesicular transport. Hydrocarbon-stapled peptides were designed based on crystal structures of Rab proteins bound to their interaction partners. These modified peptides exhibit significantly increased affinities and include a stapled peptide (StRIP3) that selectively binds to activated Rab8a and inhibits a Rab8a-effector interaction in vitro. ",

keywords = "Amino Acid Sequence, Cell Line, Drug Design, Humans, Models, Molecular, Molecular Sequence Data, Peptides, Protein Interaction Maps, rab GTP-Binding Proteins, Journal Article, Research Support, Non-U.S. Gov't",

author = "Jochen Spiegel and Cromm, {Philipp M} and Aymelt Itzen and Goody, {Roger S} and Grossmann, {Tom N} and Herbert Waldmann",

note = "Copyright {\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2014",

month = feb,

day = "24",

doi = "10.1002/anie.201308568",

language = "English",

volume = "53",

pages = "2498--503",

journal = "ANGEW CHEM INT EDIT",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

number = "9",

}

RIS

TY - JOUR

T1 - Direct targeting of Rab-GTPase-effector interactions

AU - Spiegel, Jochen

AU - Cromm, Philipp M

AU - Itzen, Aymelt

AU - Goody, Roger S

AU - Grossmann, Tom N

AU - Waldmann, Herbert

PY - 2014/2/24

Y1 - 2014/2/24

N2 - Small GTPases are molecular switches using GDP/GTP alternation to control numerous vital cellular processes. Although aberrant function and regulation of GTPases are implicated in various human diseases, direct targeting of this class of proteins has proven difficult, as GTPase signaling and regulation is mediated by extensive and shallow protein interfaces. Here we report the development of inhibitors of protein-protein interactions involving Rab proteins, a subfamily of GTPases, which are key regulators of vesicular transport. Hydrocarbon-stapled peptides were designed based on crystal structures of Rab proteins bound to their interaction partners. These modified peptides exhibit significantly increased affinities and include a stapled peptide (StRIP3) that selectively binds to activated Rab8a and inhibits a Rab8a-effector interaction in vitro.

AB - Small GTPases are molecular switches using GDP/GTP alternation to control numerous vital cellular processes. Although aberrant function and regulation of GTPases are implicated in various human diseases, direct targeting of this class of proteins has proven difficult, as GTPase signaling and regulation is mediated by extensive and shallow protein interfaces. Here we report the development of inhibitors of protein-protein interactions involving Rab proteins, a subfamily of GTPases, which are key regulators of vesicular transport. Hydrocarbon-stapled peptides were designed based on crystal structures of Rab proteins bound to their interaction partners. These modified peptides exhibit significantly increased affinities and include a stapled peptide (StRIP3) that selectively binds to activated Rab8a and inhibits a Rab8a-effector interaction in vitro.

KW - Amino Acid Sequence

KW - Cell Line

KW - Drug Design

KW - Humans

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Peptides

KW - Protein Interaction Maps

KW - rab GTP-Binding Proteins

KW - Journal Article

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

U2 - 10.1002/anie.201308568

DO - 10.1002/anie.201308568

M3 - SCORING: Journal article

C2 - 24481744

VL - 53

SP - 2498

EP - 2503

JO - ANGEW CHEM INT EDIT

JF - ANGEW CHEM INT EDIT

SN - 1433-7851

IS - 9

ER -