A NEW RADIO-THERANOSTIC AGENT CANDIDATE: SYNTHESIS AND ANALYSIS OF (ADH-1)c-EDTA CONJUGATE

作者：Ucar Burcu; Acar Tayfun; Pelit-Arayici Pelin; Demirkol Mehmet Onur; Mustafaeva Zeynep

来源：Fresenius Environmental Bulletin, 2018, 27(7): 4751-4758.

• Solid phase peptide synthesis
• macrocyclization
• conjugation
• N-cadherin
• (ADH-l)c
• cancer

The aim of this article are to synthesis, conjugate and characterize of (ADH-1)c (cell adhesion molecule) cyclic peptide sequence c(N-Ac-CHAVC-NH2) of N-CAD (N-cadherin) antagonist from a novel family of cyclic peptide antagonists. (ADH-l)c specifically targets and blocks N-cadherin, which can cause tumor vasculature disruption, inhibition of tumor cell growth, induction of tumor cell and endothelial cell apoptosis. (ADH-1)c is a cyclic pentapeptide vascular-disrupting agent with antineoplastic and antiangiogenic interactions. In peptide synthesis, microwave irradiation-assisted solid phase peptide synthesizer system with fluorenylmethyloxycarbonyl chemistry has been used to complete peptide sequences with high yields and smaller amount of racemization. macrocyclization was performed with ammonium acetate (5% w/v) following linear peptide synthesis. Conjugates of the cyclic peptide were synthesized with the EDTA chelator by application of water-soluble carbodiimide procedure. A wide range of HPLC (High Performance Liquid Chromatography) conditions for the purification of the peptides were examined by using an acetonitrile-based solvent system with CH2O2 as the ion pairing agent which has provided efficient purification. The purified peptide was characterized by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The formation mechanism, physicochemical properties and electrical charges of the synthesized conjugate was characterized by Fluorescence Spectrophotometer, Zetasizer and LC-ESI-MS.

• 出版日期2018