Department of Biopharmaceutics and

Transkrypt

Department of Biopharmaceutics and
Department of Biopharmaceutics and Pharmacodynamics
Faculty of Pharmacy, Medical University of Gdańsk
Head: Prof. Roman Kaliszan, Ph.D., D.Sc.
Corresponding Member of the Polish Academy of Sciences
Prof. Antoni Nasal, Ph.D., Barbara Damasiewicz, Ph.D., Michał Markuszewski, Ph.D.,
Aleksandra Radwańska, Ph.D., Danuta Siluk, Ph.D., Tomasz Bączek, Ph.D.,
Teresa Frąckowiak, Ph.D., Anna Wojdełko, M.Sc., Michał Marszałł, M.Sc.,
Paweł Wiczling, M.Sc., Aleksandra Dąbrowska, Ing., Janina Kozłów
Address: Gen. J. Hallera 107, 80-416 Gdańsk
Tel.: ++48 58 3493260
Fax: ++48 58 3493262
e-mail: [email protected]
Instytut Rozrodu Zwierząt i Badań Żywności PAN w Olsztynie
COLLABORATORS
Department of Chemistry, University of Edinburgh
Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt am Main
Forschungsinstitut für experimentelle Biologie und Medizin, Borstel
Department of Chemistry, Rutgers University, New Brunswick
Department of Oncology, McGill University, Montreal
Department of Chemistry, State University of New York in Binghamton
Institut für Organische Chemie, Abteilung Bioorganische Chemie, Universität Bremen
Department of Chemistry, University College London, London
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest
Laboratory of Instrumental Analysis, University of Technology, Eindhoven
LC Resources Inc., Walnut Creek, CA, USA
School of Materials Science, Toyohashi University of Technology,
Department of Polymer Science and Engineering, Kyoto Institute of Technology
Faculty of Science, Himeji Institute of Technology
PUBLICATION RECORDS
Books
Review Articles
Original Reports
Full Papers in Symposium Proceedings
Patents
Symposium Abstracts
Published book reviews, popularization of
science, etc.
Σ IF>250
Total number of citations  3.000
10
14
160
30
6
210
50
Σ 480
MEMBERSHIP OF
EDITORIAL (ADVISORY) BOARDS
- Solubility Data Series (1985 - 1992)
- Quantitative Structure-Activity Relationships (1988 - 1997)
-Biomedical Chromatography (since 1998)
- Journal of Chromatographic Science (since 2000)
- Journal of Separation Science (since 2001)
- Journal of Pharmaceutical and Biomedical Analysis (since 2001)
- Acta Chromatographica (since 1995)
-Acta Poloniae Pharmaceutica - Drug Research (since 1997)
- Annales Universitatis Mariae Curie-Skłodowska
-Annales Academiae Medicae Gedanensis
-Farmacja Polska
- Gazeta AMG
- Służba Zdrowia
- Wiadomości Farmaceutyczne
About 400 reviews of manuscripts presented to some 30
international journals
CHOICE OF STRUCTURE
H
Example: S = 20; N = 8
COOH
H
H
H
H
X = SN = X = 208 = 25 600 000 000
N - number of substitution sites
S - number of substituents
H
H
CA describes  12 000 000 compounds
Numerical descriptors
of solute structures
Chromatographic
retention parameters
Computerized statistical
data processing
QSRR
Identification of
informative
descriptors
Determination of
molecular separation
mechanism
Determination of complex
physicochemical properties
Quantitative
comparison of
columns
Evaluation of relative
biological activity
Retention
prediction
Drug:
Water/lipid partition (log P, log kw);
Degree of ionization (pKa)
Lipid
WATER
I
pH1
Drug molecules I:
neutral I + ionized I
Example:
Kanamycin: pKa = 7.2
Milk: pHI = 6.4
Blood: pH
= 7.4
II
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
WATER
II
pH1I
Drug molecules II:
neutral II + ionized II
[Drug in milk] [1 +10 pK  pH

[Drug in blood] [1 +10 pK  pH
a
milk
]
a
blood
]
 4 .5
IMMOBILIZED ARTIFICIAL MEMBRANES
Hydrophilic region
H3C
+
H3C N
H3C
O
O P O
O
O
O
O C C O
H2N
C O
H2N
N
SILICA SUPPORT
IAM.PC.(ester)
Hydrophobic region
Structure of cell membrane
H3C
+
H3C N
H3C
O
O P O
O
O
O
CH3
H3C
+
H3 C N
H3C
O
O P O
O
C O
HN
C O
N
C O
HN
C O
HN
C O
N
C O
HN
SILICA SUPPORT
SILICA SUPPORT
IAM.PC.DD.
IAM.PC.(ether)
CHROMATOGRAPHIC MODELING OF
DRUG-PROTEIN INTERACTIONS
(HSA, AGP, Melanin, Keratin, Collagen)
STERIC RESTRICTION
HYDROPHOBIC REGION
⊝ +
⊝
ANIONIC REGION⊝
HYDROPHOBIC REGION
FUTURE PROJECTS AND GOALS
- pH-Gradient HPLC: a new method of chromatographic analysis of
bioanalytes
- Metabolomics: metabolite profile differentiation using LC/CE/MS
and bioinformatics
-Analytical separation-identification platform LC-MC for the analysis
of proteomes
- Relationship between the GPIIIa gene A1/A2 polymorphism and
blood platelet response to aggregation agonists among the North
Poland population
SELECTED RECENT PUBLICATIONS
•R. Kaliszan: "Quantitative Structure-Retention Relationships (QSRR) in Chromatography",
In Encyclopedia of Separation Science, Vol III, I.D. Wilson (Ed.), Academic Press, San
Diego, 2000, pp. 4063-4075
•D. Siluk, R. Kaliszan, P. Haber, J. Petrusewicz, Z. Brzozowski, G. Sut, Antiaggregatory
activity of hypoglycaemic sulphonylureas, Diabetologia 45, 1034-1037 (2002)
•R. Kaliszan, P. Haber, T. Bączek, D. Siluk, K. Valko, Lipophilicity and pKa estimates from
gradient high-performance liquid chromatography, J. Chromatogr. A 965, 117-127 (2002)
•M. Markuszewski, R. Kaliszan, Quantitative structure-retention relationships in affinity highperformance liquid chromatography, J. Chromatogr. B 768, 55-66 (2002)
•A. Nasal, D. Siluk, R. Kaliszan, Chromatographic retention parameters in medicinal
chemistry and molecular pharmacology, Curr. Med. Chem. 10, 381-426 (2003)
•M.J. Markuszewski, P. Britz-McKibbin, S. Terabe, K. Matsuda, T. Nishioka, Determination
of pyridine and adenine nucleotide metabolites in Bacillus subtilis cell extract by sweeping
borate complexation capillary electrophoresis, J. Chromatogr. A 989, 293-301 (2003)
•T. Bączek, R. Kaliszan, Predictive approaches to gradient retention based on analyte
structural descriptors from calculation chemistry, J. Chromatogr. A 987, 29-37 (2003)