Chemical Methods for Peptide and Protein Production

Abstract

Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

Determining the Secondary Structure of Membrane Proteins and Peptides Via Electron Spin Echo Envelope Modulation (ESEEM) Spectroscopy

“…Also, unlike ribosomal protein synthesis, SPPS can proceed in both C-terminal and N-terminal fashions. SPPS has the ability to synthesize peptides with up to 70 amino acids and can potentially make proteins and peptides with 150+ amino acids with the help of chemical ligation (Chandrudu, Simerska, & Toth, 2013; Raibaut, El Mahdi, & Melnyk, 2015). The two most commonly used forms of SPPS are Fmoc and Boc, which have different protecting groups used on the C-terminal or N-terminal residues of each amino acid block.…”

Antimicrobial peptide-based treatment for endodontic infections — Biotechnological innovation in endodontics

“…Cross et al (2007) described casein phosphopeptides derived from casein protein as a market product called Recaldent™ and Tooth Mousse™ (chewing gum) acting on enamel remineralization (Cross et al, 2007). As other examples of commercialized AMP products with potential to treat general diseases, Chandrudu et al (2013) mentioned some products on the market for other purposes, such as osteoporosis, diabetes, HIV, prostate, breast and bone cancer, heart failure, multiple sclerosis, neuroendocrine tumors, hereditary angioedema, pain, and idiopathic thrombocytopenic purpura (Chandrudu et al, 2013). A list of products based on antimicrobial peptides, including the product name, test phase, active peptide, drug presentation, target and patent number is presented in Table 2.…”

Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria

“…LCPs were synthesized using microwave-assisted Boc chemistry by solid-phase peptide synthesis (SPPS) [30] at 20 W and 70°C similar to previous reports [20,31]. Briefly, the peptides were synthesized using pMBHAresin.…”