Multiple anchoring of myelopeptides on sequential oligopeptide carriers (SOC(n)): synthesis, conformation and studies in human leukemia cells.
Myelopeptides, MP-6 (Val-Asp-Pro-Pro) and MP-4 (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro), induce metabolic changes in human leukemia cells, HL-60, characteristic of the differentiation process, which should be regarded as a promising therapeutic approach in cancer and related diseases. With the aim to optimize the differentiation effect of MPs, they were coupled to the Lys-N(epsilon)H(2) groups of a sequential oligopeptide carrier Ac-(Lys-Aib-Gly)(4), SOC(4), and the constructs obtained were studied. The rigid 3(10) secondary structure of the carrier is preserved even after linkage of the MPs, which also maintain their initial conformations without interacting either with each other or with the carrier, as demonstrated by (1)H nuclear magnetic resonance (NMR) spectroscopy. It is concluded that the carrier accommodates the presentation of MPs, thus improving their differentiation effect on human leukemia cells.
Keramisanou
D
D
Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Tsikaris
V
V
Sakarellos-Daitsiotis
M
M
Sakarellos
C
C
Mikhailova
A A
AA
Strelkov
L A
LA
D000595:Amino Acid Sequence; D002250:Carbon Radioisotopes / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014316:Tritium / Q000737:chemistry
D002250:Carbon Radioisotopes; D004337:Drug Carriers; D009842:Oligopeptides; D014316:Tritium; C048617:myelopeptides; D004247:DNA