Peptides-on-demand: McGill researcher's radical new green chemistry makes the impossible possible

February 25, 2009

McGill University chemistry professor Chao-Jun (C.J.) Li is known as one of the world leading pioneers in green chemistry, an entirely new approach to the science which eschews the use of toxic, petrochemical-based solvents in favour of basic substances like water and new ways of making molecules.

The environmental benefits of the green approach are obvious and significant, but following the road less travelled is also paying off in purely scientific terms. With these alternative methods, Li and his colleagues have discovered an entirely new way of synthesizing peptides using simple reagents, a process that would be impossible in classical chemistry. Their results will be published Feb. 27 in the online edition of the Proceedings of the National Academy of Sciences (PNAS),

Peptides are short oligomer and polymer substances made up of two or more amino acids linked in a chain. Proteins - also known as polypeptides - are themselves composed of longer chains of peptides. Peptides are enormously important to biological and proteomic research, but classical chemistry provides no easy way to synthesize them, making the potential impact of this discovery very significant.

"Currently, to generate peptides you must use a peptide synthesizer, an expensive piece of high-tech equipment," explained Li, Canada Research Chair in Green Chemistry. "You need to purchase every single separate amino acid unit that makes up the peptide, and feed them into the machine one by one, which then assembles them. Every time you need a new peptide, you need to synthesize it individually from scratch."

Li's new process, by contrast, allows researchers to construct a single, simple "skeleton" peptide which can be modified into any other peptide needed with the addition of a simple reagent.

"If you want to make one peptide or 20 or even 100, you just use a different reagent each time," Li said. "If you use 20 different reagents, you get 20 different peptides."

"This could never have been discovered using the classical form of chemistry," he continued. "Every amino acid unit is very similar to every other one, and classical chemistry simply cannot differentiate one from the other."

The new method is considerably less expensive than traditional techniques, and can readily be adopted by labs anywhere in the world, Li said.

"This is really an enabling new technology," he added, "and since McGill has decided not to patent it, we're making our method available to everyone. We are paying the journal's open access fee, so anyone in the world can access the paper."

McGill University

Peptide Drug Discovery and Development
by Miguel Castanho (Editor), Nuno Santos (Editor)

Filling a real knowledge gap, this handbook and ready reference is both modern and forward-looking in its emphasis on the "bench to bedside" translational approach to drug development.
Clearly structured into three major parts, the book stakes out the boundaries of peptide drug development in the preclinical as well as clinical stages. The first part provides a general background and focuses on the characteristic strengths and weaknesses of peptide drugs. The second section contains five cases studies of peptides from diverse therapeutic fields, and the lessons to be learned from them, while the final part looks at new targets and opportunities, discussing several drug targets and diseases for which peptide drugs are currently being developed.

Fmoc Solid Phase Peptide Synthesis: A Practical Approach
by W. C. Chan (Editor), Peter D. White (Editor)

In the years since the publication of Atherton and Sheppard's volume, the technique of Fmoc solid-phase peptide synthesis has matured considerably and is now the standard approach for the routine production of peptides. The basic problems outstanding at the time of publication of this earlier work have now been, for the most part, solved. As a result, innovators in the field have focussed their efforts to develop methodologies and chemistry for the synthesis of more complex structures. The focus of this new volume is much broader, and covers not only the essential procedures for the production of linear peptides but also more advanced techniques for preparing cyclic, side-chain modified, phospho- and glycopeptides. Many other methods also deserving attention have been included: convergent...

Amino Acid and Peptide Synthesis (Oxford Chemistry Primers)
by John Jones (Author)

This is a thoroughly updated edition of one of the best selling titles in the Oxford Chemistry Primer series. John Jones provides an excellent, easy to read introduction to amino acid and peptide synthesis aimed at second and final year students. The text begins with a brief survey of the role and diversity of amino acids, peptides, and proteins in nature, and goes on to describe and explain the principal methods of chemical synthesis. With its emphasis on chemical principles and strategies rather than detailed technical matters, the book will be essential reading for all students of chemistry with an interest in this field.

Enrichment of N-terminal sulfonated peptides by a water-soluble fullerene derivative and its applications to highly efficient proteomics [An article from: Analytica Chimica Acta]
by Y.H. Lee (Author), J.W. Shin (Author), S. Ryu (Author), S.W. Lee (Author), C.H. Lee (Author), L (Author)

This digital document is a journal article from Analytica Chimica Acta, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.

Description:
Recent studies have shown that N-terminal sulfonation of tryptic peptides by various sulfonating molecules greatly improves their post-source decay processes (e.g., in matrix-assisted laser desorption ionization) or the gas phase fragmentation processes (e.g., in tandem mass spectrometer), enhancing the ability to identify their sequences de novo. In the present work, we have demonstrated that incorporation of water-soluble C"6"0-N,N-dimethylpyrrolidinium iodide selectively precipitates the 4-sulfophenyl...

Microinjecting recombinant rainbow trout Ea4-peptide of pro-IGF-I into zebrafish embryos causes abnormal development in heart, red blood cells, and ... Biochemistry and Physiology, Part C]
by C.Z. Chun (Author), T.T. Chen (Author)

This digital document is a journal article from Comparative Biochemistry and Physiology, Part C, published by Elsevier in 2007. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.

Description:
E-peptides and mature insulin-like growth factors (IGFs) are produced from pre-pro-IGFs during post-translational processing and co-secreted into the circulation. Previously, we reported that introduction of a transgene encoding the secreted form of rainbow trout (rt) Ea4-peptide or human (h) Eb-peptide into newly fertilized eggs of medaka (Oryzias latipes) and zebrafish (Danio rerio) resulted in developmental defects in heart, red blood cells and vasculature. In addition to vasculature...

A Handbook of Animal Toxins: Peptides and Proteins
by Reto Stocklin (Author)

The handbook will provide a registry of all known venomous peptides and proteins, grouping the toxins according to animal species, and according to their chemical structure. Each subchapter will feature an introduction to the chemistry of this class of toxin giving a general context, function mode of action, general chemical structure and comments. This introduction will then be followed by entries for each of the toxins. For each of the toxins there is also the SWISSPROT code given, so that direct links to the database are possible. Compiled by world experts, this in an important publication in the field of protein chemistry and biology and will be invaluable for everybody interested in animal toxins.

Pharmaceutical Formulation Development of Peptides and Proteins, Second Edition
by Lars Hovgaard (Editor), Sven Frokjaer (Editor), Marco van de Weert (Editor)

Rapid advances in recombinant DNA technology and the increasing availability of peptides and proteins with therapeutic potential poses a challenge for pharmaceutical scientists who have to formulate these compounds as drug products. The therapeutic application of peptides and proteins is limited by several problems such as lack of physical and chemical stability and lack of optimal physic-chemical properties for adequate transport through various biomembranes. This book focuses on general pharmaceutical development aspects of peptides and proteins. It includes chapters on the immunogenicity of protein pharmaceuticals and the biosimulation of pharmacokinetics and pharmacodynamics.

Amino Acids, Peptides and Proteins: Volume 37 (Specialist Periodical Reports)
by Royal Society of Chemistry (Author), Etelka Farkas (Editor), Maxim Ryadnov (Editor), Jonathan Heddle (Editor), Ferenc Hudecz (Editor), Shuguang Zhang (Editor)

In an ever-increasing domain of activity, Amino Acids, Peptides and Proteins provides an annual compilation of the world's research effort into this important area of biological chemistry. Comprising a comprehensive review of significant developments at this biology/chemistry interface, each volume opens with an overview of amino acids and their applications. Work on peptides is reviewed over several chapters, ranging from current trends in their synthesis and conformational and structural analysis, to peptidomimetics and the discovery of peptide-related molecules in nature. The application of advanced techniques in structural elucidation is incorporated into all chapters, whilst periodic chapters on metal complexes of amino acids, peptides and beta-lactams extend the scope of coverage....

Peptide Antigens: A Practical Approach (Practical Approach Series)
by G. Brian Wisdom (Editor)

Peptide antigens and their antibodies have been widely exploited for the measurement, location, and purification of oligopeptides such as peptide hormones. Recently, the use of peptides to mimic substructures of proteins has led to major expansion in the application of anti-peptide antibodies. These have been especially important in identifying the characterizing proteins which are only known by their primary structure derived from a DNA sequence. Another area of recent expansion is the use of defined peptided antigens to identify and map antibodies and T-cell receptors. This book provides information and detailed protocols for the main techniques for exploitation of peptide antigens and anti-peptide antibodies, and will interest research workers in many fields.

Peptide Nucleic Acids: Methods and Protocols (Methods in Molecular Biology)
by Peter E. Nielsen (Editor)

Peter Eigil Nielsen has assembled a critically evaluated collection of key PNA protocols that are either already well established around the world, such as PCR-clamping and in situ hybridization, or that display promise of significant future impact. Basic methods for PNA oligomer synthesis and analysis have also been included. Written by experts with hands-on in the methods they describe, these readily reproducible protocols contain detailed step-by-step instructions, tips on avoiding pitfalls and on extending the method to other situations, and introductory material explaining the theory behind the process.