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The emergence of multidrug\u2010resistant <jats:italic>Pseudomonas<\/jats:italic> strains has increased the need for new antipseudomonal agents. In this study, a series of amino group\u2010modified aminopenicillin derivatives was synthesized that have different numbers of carboxyl groups and structurally resemble carboxypenicillin\u2013ureidopenicillin hybrids, and their antipseudomonal activities were evaluated. Among the derivatives synthesized, diethylenetriaminepentaacetic acid (DTPA)\u2010modified amoxicillin (DTPA\u2010Amox) showed potent antipseudomonal activity, not only against the laboratory strain PAO1 but also against clinically isolated <jats:italic>Pseudomonas<\/jats:italic> strains that were resistant to piperacillin and carbenicillin. DTPA\u2010Amox had no obvious cytotoxic effects on cultured mammalian cells. In addition, in an in vivo model of leukopenia, DTPA\u2010Amox treatment produced a moderate but statistically significant improvement in the survival of mice with <jats:italic>P. aeruginosa<\/jats:italic> strain PAO1 infection. These data suggest that polycarboxylation by DTPA conjugation is an effective approach to enhance antipseudomonal activity of aminopenicillins.<\/jats:p>","DOI":"10.1111\/1348-0421.12930","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T15:38:55Z","timestamp":1626104335000},"page":"449-461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of potent antipseudomonal \u03b2\u2010lactams by means of polycarboxylation of aminopenicillins"],"prefix":"10.1111","volume":"65","author":[{"given":"Shahinur","family":"Akter","sequence":"first","affiliation":[{"name":"Department of Microbiology, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Migiyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medical Sciences 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