PHC 540, Spring of 1999 (Past offering of course)
Contemporary Methods in Pharmaceutical Research:1 - Biophysical approaches in pharmaceutical research, Pharmaceutical Biotechnology.

Department of Pharmaceutics, SUNY/Buffalo
School of Pharmacy

Principal Instructor:

Dr. S.V. Balasubramanian, 541 Cooke Hall, 645-2844 x245 (svb@acsu.buffalo.edu)

Course Overview

This course consists of lectures and demonstrations/MiniLabs. Introduction to biotechnology derived products and genomics, protein/peptide and gene structure and sequence search, the formulation and delivery of proteins/peptides and gene based biopharmaceuticals, and the methods for their analysis, will provide an extended theme for the course.

Topics include protein and peptide formulation, with emphasis on the importance of maintaining protein structure/conformation, physical and chemical stability, and the role of lyophilization and cryoprotectants. The course will emphasize analytical methods to study chemical stability (amino acid sequencing, mass spectroscopy) and physical stability (aggregation and precipitation), along with physical methods to study physical stability (Circular Dichroism (CD), fluorescence), peptide conformation, and transport. Laboratory demonstrations will include exercises in protein formulation by lyophilization, and evaluation of physical stability using CD, fluorescence and turbidity measurements.

PHC540 will meet twice per week.

Syllabus:

Class Topic Instructor
1
Introduction to Biotechnology (proteins, peptides and oligonucleotides based pharmaceuticals) Drs. Straubinger and Balasubramanian
2&3
Introduction to Bioinformatics, computational biophysics (Introduction to sequence annotating tools like BLAST, DNASTAR and databases like GENBANK and SWISS-PROT) Introduction to molecular modeling programs and sequence search (SYBYL, PDB) Introduction to pharmacogenomics Dr Balasubramanian
4
Introduction to Recombinant DNA technology Dr Gollnick
5
Pharmaceutical and molecular aspects of protein and peptide, gene based drugs (peptide antibiotics, protein/DNA structure and transport) Delivery issues Dr Balasubramanian
6&7
Introduction to proteins/peptides and gene: structure and forces Dr. Srikrishnan/Dr. Eliseev
8&9
Determination of higher order structures (CD, Fluorescence, NMR, FT IR, X-ray and Q.light scattering) Dr Balasubramanian
10
Determination of primary structure (LC-mass spec) Dr Wood
11
Chemical instability in protein products Dr Balasubramanian
12
Physical instability and protein folding Dr Balasubramanian
13&14
Protein formulation and freeze drying Dr Balasubramanian
15
Introduction gene based products and delivery Dr Balasubramanian
16
Biophysical characterization of gene based drugs Dr Balasubramanian

Mini Labs:

Class Topic Instructor
1
Accessing structural information and introduction to computer modeling: downloading crystal coordinates (e.g.. HIV protease inhibitors); molecular modeling of peptide drugs using SYBYL Dr Balasubramanian
2&3
Bioinformatics (Use of annotating tools;Gene Mark, DNASTAR, GCG, GeneScan, BLAST GeneFinder and use of human genome based databases GenBank and Swiss-prot) Dr Balasubramanian & Dr Bharath Jayaram
4
Lyophilization of proteins: effects of stabilizers and cryoprotectants Dr Balasubramanian
5,6&7
Protein physical stability and secondary structure: analysis by CD, FT IR Dr Balasubramanian
8
Protein physical stability and tertiary structure: analysis by Fluorescence Dr Balasubramanian
9&10
Protein aggregation and precipitation: analysis by UV absorbance, QLS and turbidity Dr Balasubramanian

1999 Spring semester: some examples of student presentations:

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