Peptide Synthesis : Protecting groups - University of Calgary
While many proteins contain cysteine residues, and some have them optimally spaced for fragment assembly, many do not, and one of the research goals in this area is the extension of these concepts to allow coupling at residues other than the ^-terminus of cysteine residues. Some success has been achieved with ligation at X-Gly and Gly-X sites (14), as well as at X-His sites (15). Another development that bodes well for the chemical synthesis of larger proteins is the adaptation of chemical ligation to solid-phase using agarose as the polymeric support. This should allow repetitive ligation of smaller fragments to generate the larger protein stepwise on the polymer.
Peptide Synthesis : Protecting groups
Before the Fmoc group became popular, the t-Boc group was commonly used for protecting the terminal amine of the peptide, requiring the use of more acid stable groups for side chain protection in orthogonal strategies. Boc groups can be added to amino acids with Di-tert-butyl dicarbonate (Boc anhydride) and a suitable base.
Liquid hydrogen fluoride is without any doubt the most commonly used reagent for the cleavage of the peptide from the resin, with concomitant cleavage of the side-chain protecting groups .
Amino Protecting Groups Stability - Organic chemistry
In order to get selectivity in the reaction, all reactive groups except the two that are desired to react can be protected transiently with chemically stable protecting groups. This is referred to as maximal protection and would be preferred, except for incomplete removal and side reactions associated with deprotection of the fully protected peptide product containing a heterogeneous set of protecting groups. In solid-phase synthesis, assembly of the correct sequence is often quite facile, but incomplete removal of the protecting groups can lead to an intractable mixture. By careful control of reaction conditions (aqueous, pH, etc.), one can eliminate some of the side-chain protection to minimize problems associated with protecting group removal. This is referred to as minimal protection and is preferred if selective acylation of the amino terminus by the carboxyl of the N-terminal peptide can be achieved.
13.10: Protecting Groups in Organic Synthesis - …
- the choice of the solvent. It will in part determine the swelling of the peptide-resin and influence the accessibility to the reactive sites; it will also have a direct effect on the kinetics of the coupling reaction.
- the steric hindrance. It is determined by the nature of the side chains R1 and R2 and of their protecting groups.
- the reactivity of the activated carboxylic acid.
Organic synthesis Protecting Groups Alcohol ..
The following protecting groups are compatible with HF cleavage: The following protecting groups are compatible with TFMSOTf cleavage: The following protecting groups are compatible with TMSOTf cleavage:
Coupling reactions in SPPS require the acylation reactions to be highly efficient to yield high-purity peptides.
Admission Essay: PEPTIDE synthesis protecting groups …
The Fourth Edition includes significant developments in protective group chemistry since 1998. In addition to incorporating new protective groups now available to the synthetic organic chemist, such as the uniquely removable 2-methoxybenzenesulfonyl group for the protection of amines, the book also covers new techniques for the formation and cleavage of existing protective groups, providing the most relevant and useful examples to illustrate each methodology. The content is organized around the functional group to be protected (ethers, acids, carbonyl groups, amines, amides, phenols, etc.), and ranges from the simplest to the most complex highly specialized protective groups.