A novel PEG-based solid support enables the synthesis of >50 amino-acid peptide thioesters and the total synthesis of a functional SUMO-1 peptide conjugate

Abstract

Bis(2-sulfanylethyl)amino PEG resin gives access to large peptide thioester segments and to functional SUMO-1 conjugates.

Accelerating chemoselective peptide bond formation using bis(2-selenylethyl)amido peptide selenoester surrogates

“…Chemical synthesis is especially useful when proteins having unusual architectures1–6 or well-defined modifications at specific sites are desirable. An application of protein chemical synthesis which is of utmost importance in biological sciences is the study of some complex post-translational modifications such as glycosylation,7 ubiquitination8–10 or sumoylation 11,12…”

“…The reaction of a SEA peptide with an N-terminal cysteinyl peptide yields a native peptide bond to cysteine and proceeds efficiently in the presence of 4-mercaptophenylacetic acid (MPAA40). The usefulness of the SEA ligation has been demonstrated by the total synthesis of several functional proteins 11,12,41–45…”

“…SEA peptides are easily accessible by the Fmoc SPPS using SEA polystyrene32,48 or PEG-based resins 11,12. We therefore sought to convert SEA peptides 1 into SeEA derivatives 5 by using the exchange reaction shown in Scheme 2, which takes advantage of the capacity of SEA amide form 1 to equilibrate in water with the SEA transient thioester form 2 29,32,49.…”

Semi-synthesis of a HGF/SF kringle one (K1) domain scaffold generates a potent in vivo MET receptor agonist

“…The linear polypeptides were produced by total chemical synthesis 34,35 using a one-pot three peptide segments assembly strategy 36,37 and folded to produce highly homogeneous material. Chemical synthesis ensured the production of proteins with an atom-by-atom control of the protein structure and of the semisynthetic scaffolds.…”

New Methods for Chemical Protein Synthesis

“…For these reasons, it is highly desirable to use the longest peptide fragments possible in the condensation reactions of a protein chemical synthesis. Currently, the synthesis of peptides longer than 50 amino acids is inefficient, giving many side products which are, in most cases, difficult to separate from the desired peptide [60]. Such limitations are most often caused either by aggregation or by various side reactions which occur under the coupling and/or deprotection reaction conditions.…”