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. Author manuscript; available in PMC: 2023 Jan 26.
Published in final edited form as: J Am Chem Soc. 2022 Jan 14;144(3):1198–1204. doi: 10.1021/jacs.1c09666

Figure 5.

Figure 5.

Analysis of the impact of nonnatural side chains on the binding affinities of MLL peptides. (A) The fragment screen yielded optimized peptide HBS II from HBS I as a starting point. (B) HBS II binds KIX with submicromolar affinity, which corresponds to a 2000-fold improvement over MLL847–858 and a 50-fold improvement over the computationally optimized Peptide I. (C) HBS helices III*–VI* with single and double side-chain fragment hits were evaluated. Each nonnatural appendage offers cumulative enhancement to peptide affinity. *Denotes fluorescently labeled peptide. The binding constants for the peptides are listed in Table S2.