title: Synthesis and functional studies of tuftsin analogs containing isopeptide bond.
abstract: In the present paper a new approach is reported, to increase the resistance of tuftsin toward enzymatic cleavage by the introduction of an isopeptide bond into the molecule. The tetrapeptides H-Lys(Thr)-Pro-Arg-OH and H-Lys(Ala)-Pro-Arg-OH, the pentapeptides H-Thr-Lys(Ala)-Pro-Arg-OH, H-Thr-Lys(Thr)-Pro-Arg-OH and H-Ala-Lys(Ala)-Pro-Arg-OH and their For- and Boc-protected derivatives were built up by stepwise elongation of the chain, using conventional solution-phase methods. Preliminary experiments confirmed that from the Lys residue in position 2 of tuftsin the alpha-peptide bond between the Thr and Lys is cleaved with a significantly higher rate by leucine aminopeptidase than the epsilon-peptide bond. Several of the isopeptide derivatives increased to a higher extent the interleukin (IL-1) secretion by monocytes than tuftsin or [Ala1]-tuftsin.
authors.affiliation: Research Group for Peptide Chemistry, Hungarian Academy of Sciences, Budapest.
authors.forename: G
authors.initials: G
authors.lastname: Mezö
authors.forename: M
authors.initials: M
authors.lastname: Szekerke
authors.forename: G
authors.initials: G
authors.lastname: Sármay
authors.forename: J
authors.initials: J
authors.lastname: Gergely
mesh_terms: D000595:Amino Acid Sequence; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000032:analysis; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D009842:Oligopeptides; D007931:Leucyl Aminopeptidase; D014405:Tuftsin