Solid phase synthesis of cyclic peptides containing muramic acid

Vlahoviček-Kahlina, Kristina (2015) Solid phase synthesis of cyclic peptides containing muramic acid. Doctoral thesis, Faculty of Science > Department of Chemistry.

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Abstract

In frame of this dissertation the peptide libraries of cyclic peptide and their linear analogs containing muramic acid (Mur) in different positions, according to biologically active sequence Leu-Ser-Lys-Leu (LSKL), were synthesized. Taking into consideration that muramic acid is a dipeptide isoster, preparation of orthogonally Fmoc-protected Mur as a building block for solid phase synthesis of natural products is of particular practical importance. Synthesis of linear glycopetpide was obtained using Fmoc-strategy solid phase peptide synthesis with O-(benzotriazol-1-yl)-1,1,3,3-tetramethylamonium hexafluorophosphat (HBTU)/1-benzotriazole (HOBt) reagents for standard amino acids and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethylamonium hexafluorophosphate (HATU)/HOBt for incorporation of Mur, on peptide synthesizer. Cyclic peptides were prepared according to the so called head-to tail cyclisation of linear peptides using manual synthesis on solid phase with HATU or benzotriaz-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) reagents. Cleavage of the peptide from solid phase gave glycopetides with benzyl protected hydroxyl group at C-1 position of Mur, which was followed by catalytic hydrogenolysis to give 6 linear heptapeptides which contain Asn (important for anchoring to resin), sequence LSKL, muramic acid on different positions (1, 2, 5, 6) which alternates with Lys. Deprotection gave 6 cyclic unprotected heptapeptides wherein the cyclization was accomplished via a carboxyl group of Asn and an amino group of Mur, Lys (side chain) or Leu. The effects on proliferation of different human tumor cell lines, antimicrobial activity and interaction with DNA of prepared compounds were investigated.

Item Type: Thesis (Doctoral thesis)
Keywords: cyclic glycopeptides, muramic acid, solid phase peptide synthesis
Supervisor: Jakas, Andreja
Date: 2015
Number of Pages: 136
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Branka Maravic
Date Deposited: 01 Jul 2015 07:48
Last Modified: 01 Jul 2015 07:48
URI: http://digre.pmf.unizg.hr/id/eprint/4072

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