Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1.
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Luckner P, Brandsch M
Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1.
Eur J Pharm Biopharm. 2005 Jan;59(1):17-24.
- PubMed ID
- 15567297 [ View in PubMed]
- Abstract
The activity of the renal peptide transporters PEPT2 and PEPT1 determines-among other factors such as metabolic stability in liver and plasma-the circulatory half-life of penicillins and cephalosporins during therapy. This study was initiated to examine systematically the interaction of beta-lactam antibiotics with PEPT2. Interaction of 31 cephalosporins and penicillins with the carrier protein was characterized by measuring their ability to inhibit the uptake of [(14)C]Gly-Sar into renal SKPT cells. Cefadroxil, cefaclor, cyclacillin, cephradine, cephalexin and moxalactam were recognized by PEPT2 with very high affinity comparable to that of natural dipeptides (K(i)=3-100microM). Ceftibuten, dicloxacillin, amoxicillin, metampicillin, cloxacillin, ampicillin, cefixime, cefamandole, oxacillin and cefmetazole interacted with PEPT2 with medium affinity (K(i)=0.1-5mM). For the other beta-lactam antibiotics studied interaction was very low or not measurable (K(i)>5mM). The affinity constants of beta-lactam antibiotics at rPEPT2 and hPEPT1 are significantly correlated, but the rank orders are not identical. Decisive differences between PEPT1 and PEPT2 recognition of the N-terminal part of the compounds became evident. Moreover, this large data set of affinity constants of beta-lactam antibiotics will be useful for structure-transport (binding) analyses of PEPT2.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Ampicillin Solute carrier family 15 member 1 Protein Humans UnknownNot Available Details Benzylpenicillin Solute carrier family 15 member 1 Protein Humans UnknownSubstrateInhibitorDetails Cefotaxime Solute carrier family 15 member 1 Protein Humans UnknownNot Available Details Ceftriaxone Solute carrier family 15 member 1 Protein Humans UnknownNot Available Details Oxacillin Solute carrier family 15 member 1 Protein Humans UnknownNot Available Details - Drug Transporters
- Binding Properties