Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: A Dual-Site Inhibitor of CBP/p300 KIX is a Selective and Effective Modulator of Myb The protein-protein interaction between the KIX motif of the transcriptional coactivator CBP/p300 and the transcriptional activator Myb is a high value target due to its established role in certain acute myeloid leukemias (AML) and potential contributions to other cancers. However, the CBP/p300 KIX domain has multiple binding sites, several structural homologues, many binding partners, and substantial conformational plasticity, making it challenging to specifically target using small molecule inhibitors. Here, we report a picomolar dual-site inhibitor (MybLL-tide) of the Myb-CBP/p300 KIX interaction. MybLL-tide has higher affinity for CBP/p300 KIX than any previously reported compounds while also possessing 16,000-fold selectivity for the CBP/p300 KIX domain over other coactivator domains. MybLL-tide blocks the association of CBP and p300 with Myb in the context of the proteome leading to inhibition of key Myb*KIX-dependent genes in AML cells. These results show that MybLL-tide is an effective, modifiable tool to selectively target the KIX domain and assess transcriptional effects in AML cells and potentially other cancers featuring aberrant Myb behavior. Additionally, the dual-site design has applicability to the other challenging coactivators that bear multiple binding surfaces
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The categories of this paper are: and
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The categories of this paper are: pharmacology
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The categories of this paper are: biology
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The categories of this paper are: cognition
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The categories of this paper are: behavior
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The categories of this paper are: synthetic
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The categories of this paper are: bioinformatics
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The categories of this paper are: genomics
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The categories of this paper are: bioengineering
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The categories of this paper are: neuroscience
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The categories of this paper are: molecular
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The categories of this paper are: cell
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The categories of this paper are: physiology
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The categories of this paper are: communication
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The categories of this paper are: systems
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The categories of this paper are: zoology