Studium vibracniho cirkularniho dichroismu biologicky zajimavych latek a jejich interakci.

In this thesis the vibrational circular dichroism spectroscopy was used to study structural arrangement of small and middle as well as large biologically interesting molecules and systems. The results obtained extend the present structural knowledge concerning the porphyrin-polypeptide aggregates, the inclusion complexes and molecular recognition of the cyclodextrins, the supramolecular self-assemblies and sol-gel phase transition processes of the brucine-porphyrin based gelators.Summary and text also in EnglishAvailable from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Induced Axial Chirality in the Biphenyl Core of the C-alpha-Tetrasubstituted alpha-Amino Acid Residue Bip and Subsequent Propagation of Chirality in (Bip)n/Val Oligopeptides.

In the dipeptides Boc-Bip-L-Val-OMe and Boc-Bip-D-Val-OMe, an induced axial chirality in the biphenyl core of the Bip residue, a conformationally labile, proatropoisomeric C\u3b1,\u3b1-disubstituted glycine, was observed by electronic CD and 1H NMR. Chiral induction is significantly higher when the Val residue is located at the C-terminal position of Bip. An outstanding phenomenon of propagation of chirality was demonstrated to occur in the related 310-helical -(Bip)n-L-Val (n = 2 126) oligopeptides by CD and vibrational CD techniques

Synthesis and Conformational Study of (Bin)n and (β-2,2-Bin)n Homopeptides Based on Atropoisomeric α- and β-Amino Acids Derived from 1,1'-Binaphthyl

M. Flegel, M. Fridkin, C. Gilon, and J. Slaninova Eds., Kenes International, Geneva, Switzerland, 2005, pp. 1015-1016

Chirospectroscopic Chatracterization of the Peptide 3-10-Helix in Aqueous Solution

M. Flegel, M. Fridkin, C. Gilon, and J. Slaninova Eds., Kenes International, Geneva, Switzerland, 2005, pp. 1077-1078

Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease

A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit A\u3b242 self-aggregation (58.6 \ub1 5.1% at 50 \u3bcM) as well as hAChE-induced A\u3b240 aggregation (48.3 \ub1 6.3% at 100 \u3bcM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia