77611-37-1Relevant articles and documents
Cyclopeptides containing the DEKS motif as conformationally restricted collagen telopeptide analogues: Synthesis and conformational analysis
Wodtke, Robert,Ruiz-Gmez, Gloria,Kuchar, Manuela,Pisabarro, M. Teresa,Novotn, Pavlina,Urbanov, Marie,Steinbach, J?rg,Pietzsch, Jens,L?ser, Reik
, p. 1878 - 1896 (2015)
The collagen telopeptides play an important role for lysyl oxidase-mediated crosslinking, a process which is deregulated during tumour progression. The DEKS motif which is located within the N-terminal telopeptide of the α1 chain of type I collagen has been suggested to adopt a βI-turn conformation upon docking to its triple-helical receptor domain, which seems to be critical for lysyl oxidase-catalysed deamination and subsequent crosslinking by Schiff-base formation. Herein, the design and synthesis of cyclic peptides which constrain the DEKS sequence in a β-turn conformation will be described. Lysine-side chain attachment to 2-chlorotrityl chloride-modified polystyrene resin followed by microwave-assisted solid-phase peptide synthesis and on-resin cyclisation allowed for an efficient access to head-to-tail cyclised DEKS-derived cyclic penta- and hexapeptides. An Nε-(4-fluorobenzoyl)lysine residue was included in the cyclopeptides to allow their potential radiolabelling with fluorine-18 for PET imaging of lysyl oxidase. Conformational analysis by 1H NMR and chiroptical (electronic and vibrational CD) spectroscopy together with MD simulations demonstrated that the concomitant incorporation of a d-proline and an additional lysine for potential radiolabel attachment accounts for a reliable induction of the desired βI-turn structure in the DEKS motif in both DMSO and water as solvents. The stabilised conformation of the cyclohexapeptide is further reflected by its resistance to trypsin-mediated degradation. In addition, the deaminated analogue containing allysine in place of lysine has been synthesised via the corresponding ε-hydroxynorleucine containing cyclohexapeptide. Both ε-hydroxynorleucine and allysine containing cyclic hexapeptides have been subjected to conformational analysis in the same manner as the lysine-based parent structure. Thus, both a conformationally restricted lysyl oxidase substrate and product have been synthetically accessed, which will enable their potential use for molecular imaging of these important enzymes.
A simple synthesis of 6-hydroxynorleucine based on the rearrangement of an N-nitrosodichloroacetamide
McCarthy, Blaine G.,Macarthur, Nicholas S.,Jakobsche, Charles E.
, p. 502 - 504 (2016/01/12)
6-Hydroxynorleucine is a versatile chemical intermediate that has found broad use in target-oriented syntheses of numerous biologically active molecules. Despite its widespread use, and despite the various strategies that have been reported for its prepar
Process for producing hydroxyamino acid derivative
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Page 3, (2008/06/13)
Provided is a method of preparing a hydroxyamino acid derivative, particularly in an optically active form thereof with high efficiency. Specifically, provided is a method of preparing hydroxyamino acid derivatives represented by Formula (I) or salts ther
