1. Synthesis, characterization, X-ray crystallography, and cytotoxicity of a cymantrene keto carboxylic acid for IR labelling of bioactive peptides on a solid support.
- Author
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Peindy N'Dongo HW, Neundorf I, Merz K, and Schatzschneider U
- Subjects
- Carboxylic Acids chemistry, Cell Line, Tumor, Enkephalins chemistry, Humans, Organometallic Compounds chemical synthesis, Peptides chemistry, Phenylalanine analogs & derivatives, Phenylalanine chemistry, Organometallic Compounds chemistry, Organometallic Compounds toxicity, Peptides chemical synthesis, Spectrophotometry, Infrared
- Abstract
Cym-CO-CH2-CH2-COOH was prepared in good yield by Friedel-Crafts reaction of cymantrene (Cym, CpMn(CO)3) with succinic anhydride for the IR labelling of peptides and fully characterized, including an X-ray structure analysis (monoclinic space group P2(1)/n, a=5.727(3)A, b=19.865(9)A, c=10.518(5)A, beta=91.211(9) degrees). The compound was isolated in pure form without the need for chromatographic work-up and subsequently used for solution-phase synthesis of a bioconjugate with phenylalanine methyl ester to allow a complete spectroscopic characterization of this model system. The cymantrene keto carboxylic acid also turned out to be a very robust marker in automated microwave-assisted solid phase peptide synthesis (SPPS). [Leu5]-enkephalin (Tyr-Gly-Gly-Phe-Leu) was prepared on a Wang resin and labelled with the cymantrene derivative on the solid support under microwave irradiation in all steps. The metal-carbonyl marker stayed intact during cleavage from the resin with concentrated trifluoroacetic acid. After simple precipitation and lyophilization, the cymantrene-enkephalin bioconjugate could be obtained in analytically pure form without the need of HPLC purification. As required, the compound is non-cytotoxic against MCF-7 cells at up to 100 microM. This protocol thus allows one to introduce organometallic IR spectroscopic labels to peptides in a very straightforward way.
- Published
- 2008
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