Synthesis and biological evaluation of a pyoverdin-beta-lactam conjugate: a new type of arginine-specific cross-linking in aqueous solution.
Arginine specific reagents such as phenylglyoxal and other alpha-dioxo compounds react with arginine side chains by forming adducts with a stoichiometry of 2:1 or a mixture of 2:1 and 1:1. These adducts are labile in neutral and slightly alkaline aqueous solution. We developed a new type of cross-linking reaction with aliphatic beta-dioxo compounds. They can be used for the well-defined, irreversible covalent attachment of molecules carrying a primary amino group to arginyl residues of water soluble peptides. The reaction proceeds under mild conditions in aqueous solution, essentially without the formation of side products. A pyoverdin-cephalexin conjugate was synthesized in order to promote its cellular uptake by Pseudomonas aeruginosa. Preliminary biological investigations of the conjugate indicated that it enters the bacterial cell via the pyoverdin-mediated iron uptake pathway.
Kinzel
O
O
Institute for Organic Chemistry, University of Cologne, Germany.
Budzikiewicz
H
H
D000215:Acylation; D001120:Arginine / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects; D002506:Cephalexin / Q000737:chemistry / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006537:Heptanoates / Q000737:chemistry; D007502:Iron Chelating Agents / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides; D010860:Pigments, Biological / Q000138:chemical synthesis* / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D014867:Water; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D006537:Heptanoates; D007502:Iron Chelating Agents; D009842:Oligopeptides; D010860:Pigments, Biological; D012996:Solutions; D047090:beta-Lactams; D014867:Water; C020804:succinylacetone; C042453:pyoverdin; D001120:Arginine; D002506:Cephalexin