Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12

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

Standard

Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12. / Madsen, Daniel; Jørgensen, Frederik P.; Palmer, Daniel; Roux, Milena E.; Olsen, Jakob V.; Bols, Mikael; Schoffelen, Sanne; Diness, Frederik; Meldal, Morten.

In: ACS Combinatorial Science, Vol. 22, No. 3, 2020, p. 156-164.

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

Harvard

Madsen, D, Jørgensen, FP, Palmer, D, Roux, ME, Olsen, JV, Bols, M, Schoffelen, S, Diness, F & Meldal, M 2020, 'Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12', ACS Combinatorial Science, vol. 22, no. 3, pp. 156-164. https://doi.org/10.1021/acscombsci.9b00197

APA

Madsen, D., Jørgensen, F. P., Palmer, D., Roux, M. E., Olsen, J. V., Bols, M., Schoffelen, S., Diness, F., & Meldal, M. (2020). Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12. ACS Combinatorial Science, 22(3), 156-164. https://doi.org/10.1021/acscombsci.9b00197

Vancouver

Madsen D, Jørgensen FP, Palmer D, Roux ME, Olsen JV, Bols M et al. Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12. ACS Combinatorial Science. 2020;22(3):156-164. https://doi.org/10.1021/acscombsci.9b00197

Author

Madsen, Daniel ; Jørgensen, Frederik P. ; Palmer, Daniel ; Roux, Milena E. ; Olsen, Jakob V. ; Bols, Mikael ; Schoffelen, Sanne ; Diness, Frederik ; Meldal, Morten. / Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12. In: ACS Combinatorial Science. 2020 ; Vol. 22, No. 3. pp. 156-164.

Bibtex

@article{22e7e02b1a714f63acd0c423372b384d,

title = "Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12",

abstract = "On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.",

keywords = "destabilizing domain, encoded beads, one-bead one-compound library, solid-phase synthesis",

author = "Daniel Madsen and J{\o}rgensen, {Frederik P.} and Daniel Palmer and Roux, {Milena E.} and Olsen, {Jakob V.} and Mikael Bols and Sanne Schoffelen and Frederik Diness and Morten Meldal",

year = "2020",

doi = "10.1021/acscombsci.9b00197",

language = "English",

volume = "22",

pages = "156--164",

journal = "ACS Combinatorial Science",

issn = "2156-8952",

publisher = "ACS Publications",

number = "3",

}

RIS

TY - JOUR

T1 - Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12

AU - Madsen, Daniel

AU - Jørgensen, Frederik P.

AU - Palmer, Daniel

AU - Roux, Milena E.

AU - Olsen, Jakob V.

AU - Bols, Mikael

AU - Schoffelen, Sanne

AU - Diness, Frederik

AU - Meldal, Morten

PY - 2020

Y1 - 2020

N2 - On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.

AB - On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.

KW - destabilizing domain

KW - encoded beads

KW - one-bead one-compound library

KW - solid-phase synthesis

U2 - 10.1021/acscombsci.9b00197

DO - 10.1021/acscombsci.9b00197

M3 - Journal article

C2 - 32027120

AN - SCOPUS:85080947059

VL - 22

SP - 156

EP - 164

JO - ACS Combinatorial Science

JF - ACS Combinatorial Science

SN - 2156-8952

IS - 3

ER -

ID: 237843368