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Printable Handouts
Navigable Slide Index
- Introduction
- Synthesis of peptides and peptidomimetics
- Why peptides and proteins?
- Some misconceptions about peptides
- Advantages of peptides
- Peptide backbone and side chains torsion angles
- The Ramachandran plot
- Biological systems are inherently dynamic
- Uses of conformational constraint
- Chi-1/Chi-2 plot for Tyr
- Needs and uses for topographical constraints
- Novel Chi constrained amino acids
- Chi-1/Chi-2 plots for Tyrosine isomers
- Solid phase synthesis considerations
- Solid supports
- Acid labile linkers
- Solid phase peptide synthesis
- Peptide synthesis: coupling reagents
- Boc strategy for solid phase peptide synthesis
- Fmoc strategy for solid phase peptide synthesis
- Strategy for peptide-targeted molecular design
- Combinatorial chemistry vs. chemical library
- Combinatorial chemistry strategy
- Obtaining statistically valid combinatorial libraries
- Methodologies that use combinatorial chemistry
- Library types
- Synthesis of hetero-bivalent ligands
- Reactions examined in chemical library format (1)
- Reactions examined in chemical library format (2)
- Combinatorial chemistry drug lead time chart
- Desired factors to control in drug design
- Working hypothesis regarding ligand design
- Applying global constraints into the peptide
- Including topographical constraints
- DPDPE binding affinity and biological potency
- Designing more potent peptide mimetics
- Peptides derived from pro-opiomelanocortin
- Important structures
- NMR structures of MT-II and SHU-9120
- Bioactivities of Agouti, SHU-9119 and MT-II
- MT-II and SHU-9119 effect on feeding behavior
- Change in body weight after 10 days on MT-II
- Frogs treated with MT-II and alpha-MSH
- Local topographical constraints
- Biological activities of b-MeTrp a-MSH analogues
- Prolonged bioactivities of MT-II analogues
- Peptide and peptidomimetic delivery through BBB
- Designed peptide ligands stable to degradation
- Modification at C-terminal
- Opioid agonist and substance P antagonist activity
- Brain distribution using in-situ perfusion technique
- Conclusions
- Why peptides will be the drugs of the future
Topics Covered
- Peptide and protein synthesis is the most robust of all synthetic chemistries
- Very large combinatorial libraries with billions of different peptides are possible
- Highly constrained peptides with specific secondary (phi/psi space) and tertiary (chi space) structures can be designed and synthesized
- Peptides stable to proteolytic degradation and able to cross BBB can be synthesized
- Peptides designed and synthesized with potent and selective bioactivities
- Many excellent drugs
- Peptide synthesis a critical tool for all aspects of chemical biology
Talk Citation
Hruby, V. (2022, August 24). Chemical synthesis of peptides and peptide libraries [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/IGZP2346.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Victor Hruby has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 41:05 min
- Update Interview Duration: 11:43 min
A selection of talks on Biochemistry
Transcript
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0:00
In this presentation, we will discuss
the chemical synthesis of peptides and peptide libraries with
special emphasis on the advantages of peptides and
peptidomimetics for exploring many critical aspects of chemical biology,
especially as it relates to structural and biological function.
0:19
Peptides and proteins are of central importance to all biological processes.
Therefore, methods for their synthesis by chemical means are of
central importance to all aspects of understanding chemical biology.
Excellent methods are available for the chemical synthesis of peptides and
peptidomimetics and have been developed to a very robust nature over the last 100 years.
In fact, peptide synthesis is perhaps the most robust of
all synthetic organic methods to prepare classes of organic compounds.
The primary focus of this discussion therefore will be on
the synthesis of peptides and peptidomimetics
that have desired biological properties which are useful for biological applications.
1:05
Why peptides and proteins?
Well, basically, because they do everything in biology.
They are the class of organic molecules that have been chosen to do all of
the necessary chemical processes which are important for biological life.
For example, they serve as the catalyst in all of
the biological processes and the structural scaffolds of most living systems.
They are the mediators of energy transduction,
so the messengers and modulators of information
transduction it both peripheral and central nervous system.
They can readily adapt their structures to recognize other structures.
They can readily incorporate all of the periodic chart into
their structures and also all of the biosphere into their structures.
They readily could change
their three-dimensional structure in response to their environment.
They have universal application to all biological processes.
There are some misconceptions about peptides as suitable drug candidates.