{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singh J"],"funding":["National Cancer Institute","NCI NIH HHS"],"pagination":["18302-18313"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12772433"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["90(51)"],"pubmed_abstract":["A new vancomycin C-terminus modification is detailed that improves antimicrobial activity, especially against vancomycin-resistant organisms. Incorporation of a C-terminus cationic guanidiniocarbonyl-pyrrole (GCP) group reinstates activity against vancomycin-resistant bacteria and further improves activity against sensitive organisms by a mechanism independent of d-Ala-d-Ala binding. The functional effects of the added GCP group are apparent in the behavior of <b>8a</b>, which exhibited pronounced improvements in activity against vancomycin-resistant bacteria relative to vancomycin (ca. 100-fold) and improved activity against sensitive organisms (ca. 10-fold), where the series (<b>8a</b>-<b>d</b>) displayed a dependence on the linker length (potency: <i>n</i> = 2 > 3 > 4 > 5), most evident against vancomycin-sensitive organisms. When combined with an added CBP peripheral modification, the activity against vancomycin-resistant organisms synergistically improved as much as 3000-fold relative to vancomycin, ca. 30-fold or better relative to <b>8a</b>, and as much as 10-fold relative to CBP-vancomycin. The beneficial effects are observed with introduction at the C-terminus, but not the N-terminus, and a focused SAR indicates they are structure (e.g., linker length) as well as site specific. These observations, along with mechanistic studies, are consistent with targeting a specific feature in the bacterial cell wall versus a nonspecific role attributable to a cationic modification, especially given its modest p<i>K</i><sub>a</sub> (7-8)."],"journal":["The Journal of organic chemistry"],"pubmed_title":["Guanidiniocarbonyl-Pyrrole (GCP) C- and N-Terminus Modifications of Vancomycin."],"pmcid":["PMC12772433"],"funding_grant_id":["CA041101","R01 CA041101"],"pubmed_authors":["Singh J","Boger DL","Chatterjee S"],"additional_accession":[]},"is_claimable":false,"name":"Guanidiniocarbonyl-Pyrrole (GCP) C- and N-Terminus Modifications of Vancomycin.","description":"A new vancomycin C-terminus modification is detailed that improves antimicrobial activity, especially against vancomycin-resistant organisms. Incorporation of a C-terminus cationic guanidiniocarbonyl-pyrrole (GCP) group reinstates activity against vancomycin-resistant bacteria and further improves activity against sensitive organisms by a mechanism independent of d-Ala-d-Ala binding. The functional effects of the added GCP group are apparent in the behavior of <b>8a</b>, which exhibited pronounced improvements in activity against vancomycin-resistant bacteria relative to vancomycin (ca. 100-fold) and improved activity against sensitive organisms (ca. 10-fold), where the series (<b>8a</b>-<b>d</b>) displayed a dependence on the linker length (potency: <i>n</i> = 2 > 3 > 4 > 5), most evident against vancomycin-sensitive organisms. When combined with an added CBP peripheral modification, the activity against vancomycin-resistant organisms synergistically improved as much as 3000-fold relative to vancomycin, ca. 30-fold or better relative to <b>8a</b>, and as much as 10-fold relative to CBP-vancomycin. The beneficial effects are observed with introduction at the C-terminus, but not the N-terminus, and a focused SAR indicates they are structure (e.g., linker length) as well as site specific. These observations, along with mechanistic studies, are consistent with targeting a specific feature in the bacterial cell wall versus a nonspecific role attributable to a cationic modification, especially given its modest p<i>K</i><sub>a</sub> (7-8).","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T10:56:39.738Z","creation":"2026-05-29T03:13:02.869Z"},"accession":"S-EPMC12772433","cross_references":{"pubmed":["41381039"],"doi":["10.1021/acs.joc.5c02760"]}}