958879-77-1

Upstream product

• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 188111-18-4 1-(tert-butyl) 2-methyl (2S,4R)-4-(acetylthio)pyrrolidine-1,2-dicarboxylate 
• 121147-93-1 (2S,4S)-2-methyl N-Boc-4-((methylsulfonyl)oxy)pyrrolidine-2-carboxylate 
• 87250-97-3 2’-methyl-2’-propanyl (1S,4S)-3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate 
• 51-35-4 4R-4-hydroxyproline 
• 87691-27-8 N-tert-butoxycarbonyl-L-cis-4-hydroxyproline 
• 132622-90-3 (2S,4S)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 132622-91-4 (4S)-1-(tert-butoxycarbonyl)-4-<(methylsulfonyl)oxy>-L-proline benzyl ester 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 87250-97-3 tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate 
• 958879-76-0 N-tert-butyloxycarbonyl-(2S,4R)-4-thioacetyl-proline benzyl ester 

Relevant academic research and scientific papers

Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates

Alpha-amanitin, an extremely toxic bicyclic octapeptide extracted from the death-cap mushroom, Amanita phalloides, is a highly selective allosteric inhibitor of RNA polymerase II. Following on growing interest in using this toxin as a payload in antibody-drug conjugates, herein we report the synthesis and biochemical evaluation of several new derivatives of this toxin to probe the role of the trans-hydroxyproline (Hyp), which is known to be critical for toxicity. This structure activity relationship (SAR) study represents the first of its kind to use various Hyp-analogs to alter the conformational and H-bonding properties of Hyp in amanitin.

Internal Activation of Peptidyl Prolyl Thioesters in Native Chemical Ligation

Prolyl thioesters have shown significantly lower reactivities in native chemical ligation (NCL) in comparison to that of the alanyl thioester. This report describes a mild and efficient internal activation protocol of peptidyl prolyl thioesters in NCL without using any thiol-based additives, where the introduction of a 4-mercaptan substituent on the C-terminal proline significantly improves the reactivity of prolyl thioesters via the formation of a bicyclic thiolactone intermediate. The kinetic data indicate that the reaction rate is comparable to that of the reported data of alanyl thioesters, and the mechanistic studies suggest that the ligation of two peptide segments proceeds through an NCL-like pathway instead of a direct aminolysis, which ensures the chemoselectivity and compatibility of various amino acid side chains. This 4-mercaptoprolyl thioester-based protocol also allows an efficient one-pot ligation-desulfurization procedure. The utility of this method has been further demonstrated in the synthesis of a proline-rich region of Wilms tumor protein 1.

Dual kinetically controlled native chemical ligation using a combination of sulfanylproline and sulfanylethylanilide peptide

Dual kinetically controlled native chemical ligation using a newly developed sulfanylproline-mediated reaction in combination with an N-sulfanylethylanilide peptide was successfully applied to a previously unreported sequential coupling of peptide fragments added simultaneously to the reaction.

Collagen mimics

Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.