Document 0123
 DOCN  M94A0123
 TI    Epithelial cell permeability of a series of peptidic HIV protease
       inhibitors: aminoterminal substituent effects.
 DT    9412
 AU    Conradi RA; Hilgers AR; Burton PS; Hester JB; Drug Delivery Systems
       Research, Upjohn Laboratories, Upjohn; Company, Kalamazoo, MI 49001.
 SO    J Drug Target. 1994;2(2):167-71. Unique Identifier : AIDSLINE
       MED/94348832
 AB    The influence of the aminoterminal substituent in a homologous series of
       tetrapeptide analogs on transport across Caco-2 cell monolayers was
       studied. In a series of pyridylcarboxamide regioisomers, the 2-pyridyl
       isomer was significantly more permeable than either the 3- or
       4-congeners. The uniqueness of this peptide was further suggested by
       examining the partitioning behavior between heptane and ethylene glycol,
       a system which has been developed as a simple estimate of the
       desolvation energy or hydrogen bonding potential of a peptide. In this
       model, the 2-isomer has a much larger partition coefficient than either
       the 3- or 4-analogs, consistent with its being less solvated than
       expected based on simple structural considerations. Factors possibly
       contributing to this decreased effective polarity could be steric
       interactions or intramolecular hydrogen bonding.
 DE    Amino Acid Sequence  Cell Membrane Permeability/*PHYSIOLOGY
       Epithelium/CYTOLOGY/METABOLISM  Human  Hydrogen Bonding  HIV Protease
       Inhibitors/CHEMISTRY/*PHARMACOKINETICS  Isomerism  Molecular Sequence
       Data  Peptides/CHEMISTRY/PHARMACOKINETICS  Tumor Cells, Cultured
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).