Water-soluble fatty acid derivatives as acylating agents for reversible lipidization of polypeptides.
A novel method allowing the conjugation of a fatty acid to a peptide or protein in aqueous buffer is described in this paper. L-Cysteinyl 2-pyridyl disulfide (CPD) (III), which was obtained by reacting L-cysteine (I) with 2,2-dithiopyridine (II), was reacted with the N-hydroxysuccinimide ester of palmitic acid (IV) to yield a water-soluble derivative of palmitic acid, termed Pal-CPD (V). Pal-CPD (V) could be reacted with a sulfhydryl-containing peptide or protein in aqueous buffer to yield the palmitic acid-derivatized conjugate (VI). The palmitic acid-derivatized Bowman-Birk protease inhibitor (BBI), synthesized using this conjugation method, was demonstrated to have 140-fold higher uptake into Caco-2 cell monolayers compared to native-BBI. The biological activity of the conjugate, as assessed using an in vitro transformation assay, was retained.
Ekrami
H M
HM
Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles 90033, USA.
Kennedy
A R
AR
Shen
W C
WC
D000215:Acylation; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D015394:Molecular Structure; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D012995:Solubility; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D010169:Palmitic Acids; D010455:Peptides; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014867:Water; D019308:Palmitic Acid; D004229:Dithiothreitol