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The renal type H+/peptide symporter PEPT2: structure-affinity relationships

  • Review Article
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Summary.

The H+/peptide cotransporter PEPT2 is expressed in a variety of organs including kidney, lung, brain, mammary gland, and eye. PEPT2 substrates are di- and tripeptides as well as peptidomimetics, such as β-lactam antibiotics. Due to the presence of PEPT2 at the bronchial epithelium, the aerosolic administration of peptide-like drugs might play a major role in future treatment of various pulmonary and systemic diseases. Moreover, PEPT2 has a significant influence on the in vivo disposition and half-life time of peptide-like drugs within the body, particularly in kidney and brain. PEPT2 is known to have similar but not identical structural requirements for substrate recognition and transport compared to PEPT1, its intestinal counterpart. In this review we compiled available affinity constants of 352 compounds, measured at different mammalian tissues and expression systems and compare the data whenever possible with those of PEPT1.

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Abbreviations

Abu:

aminobutyric acid

Ac:

acetyl

Adc:

aminododecanoic acid

Ahp:

aminoheptanoic acid

Ahx:

aminohexanoic acid

Aib:

aminoisobutyric acid

Aoc:

Aminooctanoic acid

Apt:

aminopentanoic acid

5(S) Aobh:

5(S)-Amino-4-oxo-benzenehexanoic acid

5(S), 4(R) Ahbh:

5(S)-Amino-4(R)-hydroxy-benzenehexanoic acid

5(R), 4(S) Ahbh:

5(R)-Amino-4(S)-hydroxy-benzenehexanoic acid

5(S), 4(R) Ahph:

5(S)-Amino-4(R)-hydroxy-6-phenyl-2-hexanoic acid

5(S), 4(S) Ahph:

5(S)-Amino-4(S)-hydroxy-6-phenyl-2-hexanoic acid

Boc:

tert. butyloxycarbonyl

Bz:

benzoyl

Bz(NO2):

4-nitrobenzoyl

BzBz:

4-benzoyl-benzoyl

Bzl:

benzyl

Dab:

2,4-diaminobutyric acid

Hpr:

hydroxyproline

Nle:

norleucine

OBzl:

benzyl ester

OMe:

methyl ester

Orn:

ornithine

Pac:

2-phenylacetyl

Pac(NO2):

4-nitrophenyl-acetyl

Pbu:

4-phenylbutyryl

Pbu(NO2):

4-nitro-4-phenylbutyryl

Phx:

6-phenylhexanoyl

Pip:

pipecolic acid

Ppr:

3-phenyl-propionyl

Sar:

sarcosine

Z:

benzyloxycarbonyl

Z(NO2):

4-nitrobenzyloxycarbonyl

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Authors and Affiliations

  1. Institute of Biochemistry, Department of Biochemistry/Biotechnology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

    A. Biegel, B. Hartrodt, S. Gebauer, M. Rastetter, I. Thondorf & K. Neubert

  2. Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Halle, Germany

    A. Biegel, I. Knütter, P. Luckner, K. Zebisch & M. Brandsch

  3. Molecular Nutrition Unit, Institute of Nutritional Science, Technical University of Munich, Freising-Weihenstephan, Germany

    S. Theis, G. Kottra & H. Daniel

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  1. A. Biegel
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  2. I. Knütter
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  3. B. Hartrodt
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  4. S. Gebauer
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  5. S. Theis
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  11. H. Daniel
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  12. K. Neubert
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  13. M. Brandsch
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Biegel, A., Knütter, I., Hartrodt, B. et al. The renal type H+/peptide symporter PEPT2: structure-affinity relationships. Amino Acids 31, 137–156 (2006). https://doi.org/10.1007/s00726-006-0331-0

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