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Here we report a cyclic pyrrole\/lysine polyamide (cPKP) that preferentially binds AT\u2010rich DNA, with selective recognition of ATAT and ATGT motifs. In a HeLa nuclear extract\u2010based transcription system, cPKP repressed transcription in a promoter\u2010dependent manner, showing stronger inhibition of a cytomegalovirus (CMV) core promoter than of the human c\u2010\n                    <jats:italic>MYC<\/jats:italic>\n                    promoter. RNA sequencing showed that cPKP was associated with downregulation of genes whose proximal promoters were enriched for ATAT and ATGT motifs, while causing limited perturbation of global cellular homeostasis in HeLa cells. Together, these results establish cPKP as a motif\u2010selective DNA\u2010binding scaffold that can modulate transcription in a promoter\u2010dependent manner with limited global transcriptomic perturbation in human cells.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70566","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:34:27Z","timestamp":1791614067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Motif\u2010Selective DNA Recognition and Promoter\u2010Dependent Transcriptional Repression by a Cyclic Pyrrole\/Lysine Polyamide"],"prefix":"10.1002","volume":"27","author":[{"given":"Mitsuharu","family":"Ooga","sequence":"first","affiliation":[{"name":"Department of Chemistry Graduate School of Science Kyoto University  Kyoto 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