ArticleBiochemistry2026
Phage Display Driven Identification and Computational Mapping of Macrocyclic Peptides Targeting RhoA G17V.
Article in Biochemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Mutant RhoA G17V is a clinically significant yet historically undruggable oncogenic GTPase that drives angioimmunoblastic T-cell lymphoma through a neomorphic interaction with the guanine nucleotide exchange factor Vav1. Its rigid GTPase fold, absence of deep binding pockets, and transient protein-protein interfaces have hindered conventional small-molecule approaches, creating a critical need for alternative therapeutic modalities. Here, we report a systematic strategy to target RhoA G17V using macrocyclic peptides. Two complementary phage-displayed cyclic peptide libraries, an AcrK-mediated 10-mer cyclic library and a CAmCBT-cyclized 12-mer library, were subjected to high-stringency biopanning against recombinant RhoA G17V. While the 10-mer library yielded moderate-affinity binders, the 12-mer library enabled the discovery of Z1, a macrocyclic peptide with submicromolar affinity (K
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