Next generation SICLOPPS screening for the identification of inhibitors of the HIF-1α/HIF-1β protein–protein interaction
Next generation SICLOPPS screening for the identification of inhibitors of the HIF-1α/HIF-1β protein–protein interaction
Split-intein circular ligation of proteins and peptides (SICLOPPS) is a method for generating intracellular libraries of cyclic peptides that has yielded several first-in-class inhibitors. Here, we detail a revised high-content, high-throughput SICLOPPS screening protocol that utilizes next-generation sequencing, biopanning, and computational tools to identify hits against a given protein–protein interaction. We used this platform for the identification of inhibitors of the HIF-1α/HIF-1β protein–protein interaction. The revised platform resulted in a significantly higher positive hit rate than that previously reported for SICLOPPS screens, and the identified cyclic peptides were more active in vitro and in cells than our previously reported inhibitors. The platform detailed here may be used for the identification of inhibitors of a wide range of other targets.
cluster chemistry, inhibitors, monomers, peptides and proteins, screening assays
2232-2239
McDermott, Alexander
2f71eef3-a08b-4699-bd2f-7c84c8e1a87e
Windeln, Leonie M.
86658fae-f1c6-4db0-bfbc-68211d94a03a
Valentine, Jacob S.D.
c5554f03-85d6-492c-b025-d47d83501e9d
Foster, Andrew D.
e12c139f-cb45-4bed-ae80-821e9b540f3d
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
18 October 2024
McDermott, Alexander
2f71eef3-a08b-4699-bd2f-7c84c8e1a87e
Windeln, Leonie M.
86658fae-f1c6-4db0-bfbc-68211d94a03a
Valentine, Jacob S.D.
c5554f03-85d6-492c-b025-d47d83501e9d
Foster, Andrew D.
e12c139f-cb45-4bed-ae80-821e9b540f3d
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
McDermott, Alexander, Windeln, Leonie M., Valentine, Jacob S.D., Foster, Andrew D. and Tavassoli, Ali
(2024)
Next generation SICLOPPS screening for the identification of inhibitors of the HIF-1α/HIF-1β protein–protein interaction.
ACS Chemical Biology, 19 (10), .
(doi:10.1021/acschembio.4c00494).
Abstract
Split-intein circular ligation of proteins and peptides (SICLOPPS) is a method for generating intracellular libraries of cyclic peptides that has yielded several first-in-class inhibitors. Here, we detail a revised high-content, high-throughput SICLOPPS screening protocol that utilizes next-generation sequencing, biopanning, and computational tools to identify hits against a given protein–protein interaction. We used this platform for the identification of inhibitors of the HIF-1α/HIF-1β protein–protein interaction. The revised platform resulted in a significantly higher positive hit rate than that previously reported for SICLOPPS screens, and the identified cyclic peptides were more active in vitro and in cells than our previously reported inhibitors. The platform detailed here may be used for the identification of inhibitors of a wide range of other targets.
Text
mcdermott-et-al-2024-next-generation-siclopps-screening-for-the-identification-of-inhibitors-of-the-hif-1α-hif-1β
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Accepted/In Press date: 9 September 2024
e-pub ahead of print date: 23 September 2024
Published date: 18 October 2024
Keywords:
cluster chemistry, inhibitors, monomers, peptides and proteins, screening assays
Identifiers
Local EPrints ID: 496328
URI: http://eprints.soton.ac.uk/id/eprint/496328
ISSN: 1554-8929
PURE UUID: f41184d2-eaf5-40b9-8a9a-369298138d97
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Date deposited: 12 Dec 2024 17:30
Last modified: 13 Dec 2024 03:09
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Contributors
Author:
Alexander McDermott
Author:
Leonie M. Windeln
Author:
Jacob S.D. Valentine
Author:
Andrew D. Foster
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