Solid-phase peptide synthesis: an overview focused on the preparation of biologically relevant peptides

Abstract

Tailor-made design preparation of complex peptide sequence including posttranslational modifications, fluorescent labels, unnatural amino acids are of exceptional value for biological studies of several important diseases. The possibility to obtain these molecules in sufficient amounts in relative short time is thanks to the solid-phase approach.

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

“…The N-terminal amino group and the carboxylic group of an incoming amino acid are coupled to produce the peptide bond. Bruce Merrifield was one of the pioneers of utilizing insoluble resins as support during the synthesis of peptides that could then be cleaved off at the end of process to isolate the final peptide in solution [42, 43]. Quickly these strategies were adopted in solid-phase peptide synthesis.…”

“…Even the smallest-scale GMP-grade manufacturing lot by fermentation of a recombinant organism can cost over US$ 1 million. The solid-phase method is still the manufacturing method of choice for peptide synthesis [42-44]. Current challenges exist for manufacturing peptides at large scale, which is essential for their clinical translation; additional challenges include peptide impurities and failure to detect and remove them chromatographically.…”

Natural Products as Pharmaceuticals and Sources for Lead Structures**Note: This chapter reflects the opinions of the authors, not necessarily those of the US Government

“…Currently, this compound is in phase I clinical trials. Finally, a review covering the preparation of biologically active peptides has just been published and makes interesting reading when the methods are compared with those covering the synthesis of pseudo-peptides that inhibit aspartic proteinases [187]. However, without the original identification of the transition state isostere from pepstatin, none of these compounds would have been made.…”

Solid‐Phase Synthesis of 3,4‐Dihydroquinoxalin‐2(1H)‐ones via the Cyclative Cleavage of N‐Arylated Carboxamides

“…[1] In recent decades,s olid-phase synthesish as been tuned to the synthesis of small organic molecules including heterocycles and, by doing so,i th as enabled the discovery of new synthetic steps allowing diversity-oriented synthesis. [2][3][4] We recently applied this concept to the synthesiso fn itrogen heterocycles.…”

“…[6] Wang resin is the most frequently used resin for the synthesis of peptides ands mall molecules. [1,28] TheF moc protecting group of resin-bound Fmoc-ethanolamines was cleaved using piperidine and resin-bound amineswere acylated with Fmoc-a-amino acids followed by another Fmoc group cleavage.P olymer-supported amines 9 were reacted with 2-Nos-Cls and alkylated with alcohols using the Fukuyamap rotocol [29] to yield resin 10. Exposure to DBU triggered N-arylation and afforded nitro derivatives 11.S ubsequent reductiono ft he nitro group with sodium dithionate [30] provided acyclic intermediates 12.…”