Chemistry of Peptide Synthesis

"This book provides the mechanistic basis for developing rational strategies in peptide synthesis. ...The author's unpretentious writing style belies the authoritative and sophisticated textual content. Over the course of well cross-referenced chapters, this treatise quickly transitions from offering a novice the principles of peptide science to engaging expert biochemists. The narrative flows unerringly as it guides the reader through 207 mechanism-based figures. Many such figures brilliantly superimpose the complex realities of deviant side reaction pathways onto the intended reaction course. In so doing, the study allows for the development of predictive skills in identifying a priori dead-end pathways."
"Benoiton, in the fashion of a true scholar, relishes communicating the science of peptide synthesis, a field that he has pioneered. He understands the peptide bond as only an enzyme might and, in the course of this text, has ascribed explicit personalities to amino acids, their quirks notwithstanding. This extraordinary book belongs in all academic and research environments involved in peptide chemistry."
- Kennerly S. Patrick, South Carolina College of Pharmacy, Medical University of South Carolina, in the Journal of Medicinal Chemistry, Vol. 49, No. 8 (2006)

"Leo Benoiton is an experienced peptide chemist who has made fundamental contributions to the chemistry of peptide synthesis. ...The publication of such a book is timely, and could make an important contribution to the field ... useful chemistry related to peptide synthesis is well discussed in this book, particularly in highly specialized or advanced topics such as partial epimerization (racemization), coupling methods/activation, and the molecular origins of the aggregation/insolubility of protected peptides. ..."
- Stephen Kent, Institute for Biophysical Dynamics, University of Chicago, in Angewandte Chemie, Int'l Edition, Vol. 45, No. 26 (2006)

" Despite its apparent simplicity as depicted in most textbooks, the synthesis of peptides in the many structural manifestations has many problems and pitfalls that often befuddle the synthetic chemist who has never made a peptide before. Having watched over 300 undergraduate and graduate students, postdoctoral associates, and more senior scientists, struggle with doing peptide synthesis and then having to send them to the library to read the primary literature so that they would finally "get it", the appearance of N. Leo Benoiton's Chemistry of Peptide Synthesis is a godsend. In fewer than 300 pages Professor Benoiton has distilled the essence of peptide synthesis-the strategies; the tactics; the pitfalls; the mechanisms; and so forth, as has done so in the "simple" language of synthetic and mechanistic organic chemistry. Of course one can always quibble with this point or that, argue that more could have been said or discussed about some aspect of peptide synthesis, but if you are new in peptide synthesis and want to get the "full picture" or are a more experienced peptide synthetic chemist and are branching into new aspects, there is no better place either to start your education in peptide synthesis or to become introduced to and familiar with some unfamiliar aspects of synthetic peptide chemistry than this book.
"The book consists of 8 chapters in what might be called a classical organization of the field. Chapter 1 is a short but masterful exposition of the properties of amino acids and of how these properties impact in peptide synthesis and synthetic tactics. Make sure you read this chapter before you proceed. Chapters 2, 3, and 4 carefully discuss the basic strategies and tactics in peptide synthesis primarily as developed in solution phase synthesis. Chapter 2 discusses methods for peptide bond formation; Chapter 3, protecting groups and methods of deprotection and Chapter 4, problems in chirality in peptide synthesis, how to study it, how to quantify, etc. and how to minimize side reactions. I particularly enjoyed Chapter 4-not only because the author and his group have had a major impact on our understanding of issues of chirality that arise in peptide synthesis, but also because these issues are rarely discussed in any detail in current synthetic peptide chemistry chapters. Chirality nonetheless appears as a problem more often than admitted in most peptide synthesis papers. So when it does, here is the place to read all about it. Chapter 5 provides a basic introduction to the use of solid phase peptide synthesis. It concentrates very much on the fundamentals of preparing linear peptides on a solid support. Chapter 6 provides an excellent discussion of the reactivity, protection, deprotection, and side reactions which result from the presence of the several function groups that are found in the 20 standard amino acids that make up proteins and related polypeptides. A clear exposition is given of the side reactions that can result and how they can be eliminated or minimized. This chapter is a must-read for neophytes in peptide synthesis even if they already have considerate experience in other areas of synthetic chemistry. A careful read of this chapter will prevent many problems of this chapter will prevent many problems that can arise in peptide synthesis. Chapters 7 and 8, the last two chapters in the book, discuss a number of issues that can arise in the synthesis of peptides dealing with coupling reagents, activated esters, anhydrides, mixed anhydrides, etc. These chapters contain many useful ideas and thoughts of the author that are invaluable for their usefulness and for their careful considerations.
Perhaps more could have been said about cyclic peptides: disulfides, lactams, head-to-tail cyclic peptides, lactones, etc., and the difficulties that can occur in their synthesis. And virtually nothing is said about peptide ligation chemistry or synthesis of peptide conjugates. In all fairness, however, as the author clearly states in his introduction, this book was written to expose the fundamentals of peptide synthesis. In this respect, the author has produced a superb, scholarly treatment of the subject. This book will be very useful for many years to come, and I highly recommend it to those with a need to apply peptide synthesis, or those who wish to educate themselves to the field of peptide synthesis. All readers will learn a wealth of information and obtain many useful insights along the way. It is essential reading for all of my students."
-Victor J. Hruby, Regents Professor of Chemistry, Department of Chemistry, University of Arizona, Tucson, USA, written in PeptideScience, Vol. 88, No. 6 (November 2007)