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Synthesis and biological evaluation of a pyoverdin-β-lactam conjugate: a new type of arginine-specific cross-linking in aqueous solution

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  • To cite this article:

    Kinzel, O. & Budzikiewicz, H. (1999) Synthesis and biological evaluation of a pyoverdin-β-lactam conjugate: a new type of arginine-specific cross-linking in aqueous solution. J. Peptide Res.53, 618–625.


Professor Dr H. Budzikiewicz
Institute for Organic Chemistry
Greinstraße 4
D-50939 Köln
Germany
Tel. + 49–221–4704269
Fax: + 49-221-4705057
E-mail:aco88@rrz.uni-koeln.de

Abstract

Abstract: Arginine specific reagents such as phenylglyoxal and other α-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 β-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.

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