Multiple anchoring of myelopeptides on sequential oligopeptide carriers (SOCn): synthesis, conformation and studies in human leukemia cells

• Published in: The journal of peptide research 2002-09, Vol.60 (3), p.178-185
• Main Authors: Keramisanou, D., Tsikaris, V., Sakarellos-Daitsiotis, M., Sakarellos, C., Mikhailova, A. A., Strelkov, L. A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Carbon Radioisotopes - chemistry; Cell Differentiation - drug effects; cell differentiation process and myelopeptides; DNA - biosynthesis; DNA - chemistry; Dose-Response Relationship, Drug; Drug Carriers; HL-60 Cells; Humans; Leukemia - drug therapy; Leukemia - pathology; myelopeptides; myelopeptides conjugated to the sequential oligopeptide carriers; nuclear magnetic resonance of myelopeptides; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; Oligopeptides - metabolism; Protein Binding; Protein Conformation; Tritium - chemistry
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1034/j.1399-3011.2002.21017.x

: 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‐NεH2 groups of a sequential oligopeptide carrier Ac‐(Lys‐Aib‐Gly)4, SOC4, and the constructs obtained were studied. The rigid 310 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 1H 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.