Combinatorial Chemistry Course

Prof. Abraham Warshawsky (home page)

Outline of the Course

The material includes three parts

Part 1: A general out line of the course given at the Feinberg Graduate School of the Weizmann Institute of Science (WIS)
Part 2: Syllabus of the course given at the WIS
Part 3: An outline of a full course to be given in collaboration with scientists using combinatorial technologies in industrial settings.

Scope of the course

This course is a pioneering course in Israeli universities. The teaching staff includes leading scientists from academia and leading specialists who work in high-tech companies, applying combinatorial chemistry and drug development. The course aims to provide access to equipment presented by companies producing and selling combinatorial chemistry equipment.
Participants in the course will be able to obtain theoretical knowledge combined with practical expertise and access to buy their own state-of-the-art equipment package at a very reasonable cost.

Part 1: Outline of the course on Combinatorial Technologies at the WIS
Targeted Audience

The course is directed for M.Sc. and Ph.D. students of the Feinberg Graduate School of the Weizmann institute of Science working in the fields of chemistry, biology and material sciences and others who want to learn about this fast-growing field.

Objectives

The objective of this course is to provide comprehensive understanding of this fast growing field in science and technology starting from basic principles to the point of application in various fields of chemistry, biotechnology, drug development and material science.

The Lecturers

Prof. Warshawsky has a record of pioneering research work in the field of polymer-supported reactions, separation and catalysis and metal ion coordination, separation and bioapplications. He served as Editor-in-Chief of the Elsevier journals Reactive Polymers (91-95) and Reactive & Functional Polymers (96-99), and chaired two conferences in the series Polymer-Supported Reactions in Organic Chemistry: POC-86 and POC-98. Since 1991 he has served on the board of the Mediterranean Network of Polymer Science & Technology (MEDNET). He has also a record of consulting with major chemical and biotechnological companies. He is currently lecturing on combinatorial technologies and polymer-supported reactions, separation and catalysis at the Feinberg Graduate School of the Weizmann institute of Science and also in the USA and Europe.

Course Outline

Laying the Foundations: Pioneering work in the 1960s/1970s on polymer-supported reactions in urganic chemistry
Principle no. 1: Products-on-beads may be separated from reagents in solution - this is a great leap forward! From polymer-supported reactions to solid-phase-peptide synthesis (SPPS): the discovery of automated synthesis and its application in biological research, for which Prof. R.B. Merrifield was awarded the Noble Prize in 1984.
Principle no. 2:Large biomacromolecules may be assembled automatically and fast on a small bead made of synthetic polymers. This is the no-turn-back point; from now on the most important synthetic work in biology will take place on solid-supports. Understanding the role of the polymer support as the key tool in the SPPS. Intertwining the roles of polymer-functionality-reactivity-size-matrix structure-porosity. All these to better understand and improve the assembly of a growing polypeptide chain inside a polymeric porous bead. The physical parameters of polymer beads are highlighted. Polymeric reagents may be mixed together and coexist - wolf and lamb can coexist! Each performs its function separately from the other. They can then be separated from each other, e.g., due to density variations, then remixed! Separated, remixed to fulfil their reactivity duty, separated, remixed and so forth! The principle of polymer mixing is discovered - the goldmine waiting ahead at the next summit! The ball rolls back - polymers may be mixed and separated, but this game now is dead serious! If the mixing and separation is done in the combine-synthesize-spilt mode, the combinatorial technology principle is born! Random-libraries on single beads are here!
Principle no. 3:Polymer-supported-libraries of analogous compounds are being assembled simultaneously very quickly! The gains are tremendous! Breakthrough in new drug development: new companies set up to discover and produce new drug candidates.
Principle no. 4:Automatization of the synthetic process: new robots, new analytical ultrasensative methods for separation and compound identification.

Problems and further developments

The practice of organic and inorganic synthesis will never be the same again. Familiarity with combinatorial technologies also introduces some questions: the risks are there; scientific certainties may be sacrificed in favor of fast work. How can we protect the absolute scientific validity of millions of new compounds? How can they be recorded accurately? How can the "End User" of those compounds be absolutely sure of their identity? How can a company protect its work with patents? These are some of the important questions posed by the revolution of combinatorial chemistry.

Course Highlights

The course will present the main points discussed above, but having limited time, will highlight certain points of particular interest to chemists and biologists, such as drug development and screening. Specific examples of recent, important publications will be discussed. Bibliography and selected reading: such a list will be presented on the home page of this course and is now in preparation.

Part 2: Syllabus of Course on Combinatorial Technologies

Syllabus The course will be presented in 15 meetings. It will require very limited familiarity with polymer science, particularly with functional polymers. The course will require seminary presentations.

Introduction to reactive and functional polymers
Functional bead shaped materials - synthesis and characterization
Polymer-supported reactions versus solution-phase reactions
Automated synthesis - the breakthrough point
Synthesis of polypeptides, polynucleotides
Combinatorial chemistry - principles
Combinatorial chemistry - methods
Combinatorial chemistry - drug design and combinatorial methodology
Design of new materials by combinatorial chemistry
Design of new catalysts by combinatorial chemistry
Possible limitations of combinatorial chemistry
Redesigning combinatorial technology - from here to the unknown

Part 3:Full-course outline in collaboration with Dr. Gary Gellerman

Forecast and collaborations
Business outlook
Attrition of candidates on the R & D process
The drug design cycle
Current strategies in drug research
Combinatorial chemistry in drug research - thesis
Drug-like properties, similarity versus diversity
Lipinsky "five"
Drug discovery using large encoded libraries
Rational drug design, SAR and QSAR
The discovery process
Strategy, requirements and criteria for library design
High throughput compound production (HTCP)
Issues for HTCP
What are we trying to automate?
Array synthetic process
Automated synthesis
Post synthetic problem
Post synthetic solution: LLE, SPE and HT purification
Post purification process
Cheminformatics and administration
QC requirements
Submission to screen
HT Screen
Automation - benefits and drawbacks
Examples
Perspective

For a description of the slides, download MS PowerPoint file here.

Send any enquiries to A. Warshawsky cowarsha@wicc.weizmann.ac.il

Visit the Israel Society for Combinatorial Technologies (ISCT) web site

This file was last modified on Tuesday, 19-Jun-2001 12:16:20 IDT.

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