Summer School on CHEMICAL BIOLOGY OF GPCR LIGANDS
Prof. Dr. Annette G. Beck-Sickinger
(Leipzig University, Institute of Biochemistry)
21-28 July 2014, Vanderbilt University
Many ligands of GPCR belong to the family of peptides and proteins. This includes all class B GPCR ligands, e. g. calcitonin, glucagon and the pharmacologically relevant GLP-1, from which modified analogies have entered the anti-diabetic market recently (e. g. Exenentide, Liraglutide, etc.). But also in the family of class A GPCR different peptide and protein hormones (angiotensin, bradykinin, chemokines, FSH, etc.) play an important role in physiology.
Peptide ligands have some unique properties. They can be obtained by solid phase peptide synthesis and chemically modified with specific side-chain protection strategies. This includes selective labeling with fluorescent dyes, radioactive tracers, biotin, EPR- or NMR- probes to study their biophysical and structural properties. Furthermore, to overcome the proteolytic lability of peptides, modifications like lipidation or PEGylation have been successfully introduced to obtain drugs that are on the market. Protein ligands are usually produced recombinantly and accordingly modification are limited to the 20 proteinogenic amino acids by classical techniques. Novel methods like mis-charging of tRNA and chemical ligation strategies will be discussed that allow including non-natural amino acids into proteins. By using expressed protein ligation a combination of recombinant production and solid phase synthesis leads to protein with full segments replaced by solid phase synthesis and accordingly semi-synthetic protein production.
The course will introduce students to these novel techniques and explain the methods with examples from different type of peptide and protein ligands. Application in the field of structural biology, biophysical analysis, biotechnology, biomedicine, molecular pharmacology, oncology, and cell biology will be shown. Synthesis and application of molecular probes to answer biological questions, including their introduction into proteins, combinatoric strategies, high throughput screening and drug design in pharmaceutical and biotechnological industry. Immobilization of biomolecules for novel biomaterials, implants and drug release systems will be discussed. Furthermore peptide and protein drugs will be introduced and discussed with respect to modification, stability and selectivity.
Students who wish to take the class for credit should register. Students, postdocs, and faculty who wish to audit the class are welcome. Please send a note to Jens Meiler ().