Salicylaldehyde Esters Research Articles

Serine/Threonine Ligation in Cyclizing Peptides

The increasing demands for the synthetic peptides and proteins have greatly advanced the method and strategy of chemical synthesis. In this Synpacts article, we will share our new ligation concept, serine/threonine ligation (STL), and the application in the synthesis of cyclic peptides, particularly backbone-constrained ­cyclic tetrapeptides. This ligation relies on the chemoselective reaction between N-terminal serine/threonine and a C-terminal salicylaldehyde ester.

Semisynthesis of Peptoid–Protein Hybrids by Chemical Ligation at Serine

Chemical ligation protocols were explored for generating semisynthetic peptoid-protein hybrid architectures containing a native serine residue at the ligation site. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to the N-terminus of the RNase S protein or the therapeutic hormone PTH(1-34) polypeptide. This technique will expand the repertoire of strategies to enable design of hybrid macromolecules with novel structures and functions not accessible to fully biosynthesized proteins.

Development and application of serine/threonine ligation for synthetic protein chemistry.

Chemical synthesis of proteins, especially those with post-translational modifications, has offered new opportunities to study the protein structure-function relationship. In the past four years, we have developed the serine/threonine ligation (STL), which involves the chemoselective reaction between peptide salicylaldehyde esters and peptides with N-terminal serine or threonine. The method has been successfully applied to the synthesis of both linear and cyclic peptides/proteins.

Facile Synthesis of Peptidyl Salicylaldehyde Esters and Its Use in Cyclic Peptide Synthesis

An efficient solid phase synthetic protocol for salicylaldehyde ester peptides is reported. With a Ser or Thr at the N-terminus, these salicylaldehyde ester peptides can be easily converted to Ser/Thr containing cyclic peptides.

Protein chemical synthesis by serine and threonine ligation

An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides--ovine-corticoliberin and Forteo--and the human erythrocyte acylphosphatase protein (∼11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc-solid-phase peptide synthesis.

Synthesis of human growth hormone-releasing hormone via three-fragment serine/threonine ligation (STL)

The synthesis of human growth hormone-releasing hormone (hGH-RH), by the chemoselective serine/threonine ligations (STLs) of three unprotected peptide fragments, is reported. To allow for the multiple-fragment ligation, we chose the Msz (p-(methylsulfinyl)benzyloxycarbonyl) group, which is compatible with the preparation of peptide salicylaldehyde esters via Fmoc-SPPS and readily removed by reductive acidolysis, to protect the serine and threonine residue at the N-terminus.

Chemoselective fragment condensation between peptide and peptidomimetic oligomers

We report the first example of chemoselective fragment condensation, through native amide bond formation, between peptoid and peptide oligomers. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to peptides containing N-terminal serine or threonine residues. We investigate the ligation efficiency of peptoid oligomers varying in length, sequence, and C-terminal steric bulk. These protocols enhance accessibility of structurally complex peptoid-peptide hybrids and will facilitate the design new semi-synthetic proteins with unique attributes.

Acylcobalt salophen complexes. Homolytic decomposition to salicyl aldehyde esters

Irradiation of acylcobalt salophen complexes leads to salicyl aldehyde ester products resulting from cobalt-to-oxygen migration.

Exchange reactions of zirconium tetrakisacetylacetonate

1. On the basis of a study of the reaction of zirconium tetrakisacetylactonate under anhydrous conditions with butyl and benzyl alcohols, benzoylacetone, salicylaldehyde, and acetoacetic ester it was shown that chelate groups of one sort can be completely replaced by chelate groups of a different sort and also by alkoxy and benzyloxy groups. 2. By this method the syntheses were performed of butyl orthozirconate and the following previously undescribed compounds: 3. Reaction between equimolecular proportions of zirconium tetrakisacetylacetonate and acetyl chloride gave zirconium trisacetylacetonate chloride (C5H7O2)3ZrCl and similarly, zirconium tetrakisbenzoylacetonate gave zirconium trisbenzoylacetonate chloride (C10H9O2)3ZrCl.