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Design principles for cyclin K molecular glue degraders (Nature Chemical Biology, 2023)

Z. Kozicka, D. Suchyta, V. Focht, G. Kempf, G. Petzold, M. Jentzsch, C. Zou, C. Di Genua, K. Donovan, S. Coomar, M. Cigler, C. Mayor-Ruiz, J. Schmid-Burgk, D. Häussinger, G. Winter, E. Fischer, M. Słabicki, D. Gillingham, B, Ebert, N. Thomä

In this manuscript, we delve deep into the unexpected diversity of cyclin K degraders and solve 28 ternary complex crystal structures to understand how structurally dissimilar compounds can bring the same proteins together.

For a short digest, see also: the associated research briefing

Unravelling molecular glue degrader diversity (Nature Chemical Biology, 2023)

Z. Kozicka, N. Thomä


Prize essay summarising my PhD work on cyclin K degraders

Gluing the pieces together

(Science, 2023)

Z. Kozicka

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Readout of histone methylation by Trim24 locally restricts chromatin opening by p53 (Nature Structural and Molecular Biology, 2023)

L. Isbel, I. Murat, S. Durdu, R. S. Grand, J. Weiss, E. Pfeiffer, Z. Kozicka, A. K. Michael, L. Burger, N. H. Thomä, D. Schübeler

This work looks into how the transcription factor and tumour suppressor p53 is modulated by its chromatin-sensitive cofactor Trim24.

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Haven't got a glue: Protein surface variation for the design of molecular glue degraders (Cell Chemical Biology, 2021)

Z. Kozicka, N. Thomä

In this review, we outline a novel conceptual framework for small-molecular degrader compounds and discuss strategies for rational discovery and design of degraders.

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The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K (Nature, 2020)

M. Słabicki*, Z. Kozicka*, G. Petzold*, Y.-D. Li, M. Manojkumar, R. Bunker, K. Donovan, Q. Sievers, J. Koeppel, D. Suchyta, A. Sperling, E. Fink, J. Gasser, L. Wang, S. Corsello, R. Sellar, M. Jan, D. Gillingham, C. Scholl, S. Fröhling, T. Golub, E. Fischer, N. Thomä†, B. Ebert†

(*equal contribution)

In this publication, we describe the discovery of the mode of action of CR8, a kinase inhibitor and a molecular glue degrader of cyclin K, through a target- and ligase-agnostic degrader search.  

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Rational discovery of molecular glue degraders via scalable chemical profiling (Nature Chemical Biology, 2020)

C. Mayor-Ruiz, S. Bauer, M. Brand, Z. Kozicka, M. Siklos, H. Imrichova, I. Kaltheuner, E. Hahn, K. Seiler, A. Koren, G. Petzold, M. Fellner, C. Bock, A. Muller, J. Zuber, M. Geyer, N. Thomä, S. Kubicek, G. Winter

This publication outlines another method for target- and ligase-agnostic molecular glue degrader search and identifies degraders of RMB39 and cyclin K. 

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Taking the brakes off targeted protein degradation (Cell Chemical Biology, 2020)

Z. Kozicka, G. Petzold, N. Thomä

In this preview, we profile a paper by Petrilli et al. that describes a proof-of-concept PCSK9 degrader. 


Mechanisms of OCT4-SOX2 motif readout on nucleosomes (Science, 2020)

A. Michael*, R. Grant*, L. Isbel*, S. Cavadini, Z. Kozicka, R. Bunker, A. Schenk, A. Graff-Meyer, G. Pathare, J. Weiss, S. Matsumoto, L. Burger, D. Schübeler†, N. Thomä†

This work explores how transcription factors can access their motifs in the context of chromatinized DNA. 

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Structural mechanism of cGAS inhibition by the nucleosome (Nature, 2020)

G. Pathare, A. Decout, S. Glück, S. Cavadini, K. Makasheva, R. Hovius, G. Kempf, J. Weiss, Z. Kozicka, B. Guey, P. Melenec, B. Fierz, N. Thomä†, A. Ablasser† 

This publication outlines the structural basis for why the immune sensor cGas is not activated by nuclear DNA.  

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