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A peptide is described that contains the 37 N-terminal amino acids of the mouse Arf protein and is capable of arresting the cell cycle. Arf is a tumor suppressor that regulates the p53 protein.

A study was conducted on AAC(6')-Ii-bound conformations of isepamicin and butirosin A as determined by transferred nuclear Overhauser effect spectroscopy and molecular modeling. The findings indicate that isepamicin adopts two different conformations in the AAC(6')-Ii.CoA.isepamicin ternary complex. In contrast, butirosin A adopts a single conformation in the AAC(6')-Ii.CoA.butirosin A ternary complex. Moreover, aminoglycosides with 4,6- and 4,5-disubstituted 2-deoxystreptamine rings bind to AAC(6')-Ii with different conformations.

Aberrant gene activation driven by the histone acetyltransferases p300 and CREB binding protein (CBP) has been linked to several diseases, including cancers. Because of this, many efforts have been aimed toward the targeting of the closely related paralogues, p300 and CBP, but these endeavors have been exclusively directed toward noncovalent inhibitors. X-ray crystallography of A-485 revealed that both p300 and CBP possess a cysteine (C1450) near the active site, thus rendering covalent inhibition an attractive chemical approach. Herein we report the development of compound 2 , an acrylamide-based inhibitor of p300/CBP that forms a covalent adduct with C1450. We demonstrated using mass spectrometry that compound 2 selectively targets C1450, and we also validated covalent binding using kinetics experiments and cellular washout studies. The discovery of covalent inhibitor 2 gives us a unique tool for the study of p300/CBP biology., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)