title: Synthesis of oligotuftsin-based branched oligopeptide conjugates for chemotactic drug targeting.
abstract: The synthesis and chemotactic properties of a new class of branched oligopeptide-based conjugates are described. Tetratuftsin derivatives containing chemotactic formyl tripeptides (For-MLF, For-NleLF or For-MMM) in branches were prepared by stepwise solid-phase peptide synthesis. The influence of the composition and ionic charge of the carrier-branched oligopeptide on the chemotactic behaviour of the conjugate was studied in Tetrahymena pyriformis. Conjugates with methotrexate (Mtx) as a drug component was also prepared. For this, a GFLGC spacer, cleavable by cathepsin B, was used. The spacer with N-terminal methotrexate was coupled to the chloroacetylated chemotactic carrier molecule by thioether bond formation. The chemotactic activity and cytotoxity of Mtx conjugates were also studied.
authors.affiliation: Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, 1518 Budapest, Hungary. hogyishivjak@yahoo.com
authors.forename: Gábor
authors.initials: G
authors.lastname: Mezö
authors.forename: Orsolya
authors.initials: O
authors.lastname: Láng
authors.forename: Annamária
authors.initials: A
authors.lastname: Jakab
authors.forename: Katalin B
authors.initials: KB
authors.lastname: Bai
authors.forename: Ildikó
authors.initials: I
authors.lastname: Szabó
authors.forename: Gitta
authors.initials: G
authors.lastname: Schlosser
authors.forename: Julianna
authors.initials: J
authors.lastname: Láng
authors.forename: László
authors.initials: L
authors.lastname: Köhidai
authors.forename: Ferenc
authors.initials: F
authors.lastname: Hudecz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013769:Tetrahymena pyriformis / Q000187:drug effects; D014405:Tuftsin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002630:Chemotactic Factors; D005493:Folic Acid Antagonists; D009842:Oligopeptides; D014405:Tuftsin; D008727:Methotrexate