4th EucheMs chemistry congress

Poster Session 1
s902
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - life sciences
P - 0 0 8 4
CoBALt-BindinG CAPACity of the Bovine
SeruM ALBuMin treAted in vitro By vAriouS
oxidizinG AGentS
v. zAitSev 1 , e. LituS 1 , A. zhdAnovA 2 ,
n. KoSterinA 1 , A. ryAKShinA 1
1 Volgograd State Medical University, Basic and Clinical
Biochemistry, Volgograd, Russia
2 Volgograd State Medical University, University Clinic no.1,
Volgograd, Russia
Various properties of the serum albumin are often used as
basis of a number of clinical laboratory tests. One of them is the
ACB test proposed by Bar-Or et al. to detect myocardial ischemia.
Hypothesis which underlies this test is reduction of the serum
albumin cobalt-binding capacity (CoBC) due to oxidative
modification during the blood passes through hypoxic
myocardium. However, genuine ‘ishemia-modified albumin’
(IMA) has not been purified yet. Moreover, controversal data
about clinical significance of the ACB test has risen. We proposed
diagnostic ambiguity of the ACB test might be concerned with
IMA propeties which have not determinated clearly. We examined
whether various oxidizing agents could change CoBC of the
serum albumin diversely. The bovine serum albumin (BSA) was
used as model protein. We measured CoBC by colourimetric
dithiothreitol assay. The tested oxidizing agents were the Fenton’s
reagents and NaOCl. All tested oxidizing agents caused weak
accumulation of dinitrophenylhydrazine-reactive carbonyls and
depletion of the thiol groups in BSA. However, effects of
oxidizing agents on CoBC were different. The copper-based
Fenton’s reagent (H O + CuSO ) significantly reduced CoBC of
2 2 4
treated BSA in comparison with native BSA. Effect of the
iron-based Fenton’s reagent (H O + Mohr’s salt) on CoBC was
2 2
negligible. On the contrary, treatment of BSA by NaOCl increased
CoBC value. Although the effect of NaOCl seems surprising,
the chemical modification of ε-NH -groups of Lys by
2
acetylation, deamination, succinylation, or reaction with
2,4-dinitrobenzenesulphonic acid is known to raise the cobalt
binding by human serum albumin. Similarly NaOCl modifies
ε-NH -group of Lys forming the chloramine groups. We suppose
2
the NaOCl-induced increase of BSA CoBC can be produced by
elimination of positive charges of lysines in the protein molecule.
Hence, we showed oxidants can act as both inhibitors and
stimulants of cobalt-binding activity of serum albumin.
Keywords: Proteins; Oxidation; Redox chemistry;
4 th EucheMs chemistry congress
P - 0 0 8 5
SyntheSiS And StruCture-ACtivity
reLAtionShiPS of BiS-3-ChLoroPiPeridineS
AS BifunCtionAL dnA ALKyLAtinG AGentS
i. zurAvKA 1 , r. GÖttLiCh 1 , A. PinGoud 2 , w. wende 2 ,
e. PetzinGer 3 , J. Geyer 3 , e. eSSid 3
1 Justus-Liebig-University Giessen, Institute of Organic
Chemistry, Giessen, Germany
2 Justus-Liebig-University Giessen, Institute of Biochemistry,
Giessen, Germany
3 Justus-Liebig-University Giessen, Institute of Pharmacology
and Toxicology Faculty of Veterinary Medicine, Giessen,
Germany
Bifunctional alkylating agents such as chlorambucil and
melphalan represent an important class of clinical cancer
chemotherapeutics. The antitumor antibiotics azinomycin A and
B have the ability to alkylate and cross-link DNA. However, their
poor chemical stability suggests that these natural products are
unlikely to progress as therapeutic candidates. Yet they can act as
lead structures from which to develop potentially useful new
molecules. [1]
Due to our interest in developing more effective bifunctional
alkylating agents, we designed novel bis-3-chloropiperidines
based upon the azinomycins backbone. [2] The nitrogen mustard
moiety is more stable and the alkylating functions generated via
intermediate aziridinium ions are positioned in a similar distance
as has been observed for the azinomycins. [3, 4] To examine the
relationship between structural modifications and DNA alkylating
rates it appeared appealing to introduce aromatic units that might
facilitate DNA interactions. Accordingly, we synthesised a series
of derivatives and evaluated the alkylating properties by
performing a DNA cleavage assay. Furthermore, in vitro cell
cytotoxicity studies of these compounds were carried out using
the MTT method. The biochemical and cytotoxicity results as well
as the synthetic approach to bis-3-chloropiperidines will be
presented.
references:
1. Watanabe, C. M. H. et al. Nat. Prod. Rep., 2011, 28, 693.
2. Roesmann, R., Dissertation 2008,
Justus-Liebig-University Giessen.
3. Shipman, M. et al. Organic Letters, 2004, 6, 3505.
4. Searcey M. et al. Org. Biomol. Chem., 2005, 3, 3585.
Keywords: Antitumor agents; DNA cleavage; Structure-activity
relationships;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc