Synthesis of oligotuftsin-based branched oligopeptide conjugates for chemotactic drug targeting.
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.
Mezö
Gábor
G
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, 1518 Budapest, Hungary. hogyishivjak@yahoo.com
Láng
Orsolya
O
Jakab
Annamária
A
Bai
Katalin B
KB
Szabó
Ildikó
I
Schlosser
Gitta
G
Láng
Julianna
J
Köhidai
László
L
Hudecz
Ferenc
F
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
D002630:Chemotactic Factors; D005493:Folic Acid Antagonists; D009842:Oligopeptides; D014405:Tuftsin; D008727:Methotrexate