Examination of mercaptobenzyl sulfonates as catalysts for native chemical ligation: application to the assembly of a glycosylated Glucagon-Like Peptide 1 (GLP-1) analogue

Abstract

3/4-Mercaptobenzyl sulfonates were investigated as aryl thiol catalysts for native chemical ligation (NCL). Whilst catalysing NCL processes at a similar rate to 4-mercaptophenyl acetic acid (MPAA), the increased polarity and solubility of 3-mercaptobenzyl sulfonate in particular may favour its selection as NCL catalyst in many instances.

Imidazole‐Aided Native Chemical Ligation: Imidazole as a One‐Pot Desulfurization‐Amenable Non‐Thiol‐Type Alternative to 4‐Mercaptophenylacetic Acid

“…Here, we report for the first time that imidazole can be adopteda sa na lternative to MPAA in NCL using ap eptide-alkylthioester.T he efficiency of the imidazole-aided NCL (Im-NCL) is similart ot hat of traditional MPAA-aided NCL. [6] Thus, NCL product isolated by preparative RP-HPLCissometimes contaminated with MPAA, particularly after large-scale purification. [1] Since then, various bioactive proteinsh ave been prepared using NCL.…”

“…The NCL-based methodology has been appliedw idely because peptide-alkylthioesters can be readily synthesized by Bocs olid-phase peptide synthesis (SPPS,B oc = tert-butoxycarbonyl) [3] or,a ss hown recently, thioester equivalents can also be prepared by Fmoc SPPS. [6] Thus, NCL product isolated by preparative RP-HPLCissometimes contaminated with MPAA, particularly after large-scale purification. [6] Thus, NCL product isolated by preparative RP-HPLCissometimes contaminated with MPAA, particularly after large-scale purification.…”

Combination of Thiol‐Additive‐Free Native Chemical Ligation/Desulfurization and Intentional Replacement of Alanine with Cysteine

“…We synthesized stresscopin-related peptidea nd neuroendocrine regulatory peptide-2 (NERP-2) by this method. [4] In order to overcome this problem,s everal groups have developedt echniques for the removal of MPAA from reaction mixtures (liquid-liquide xtraction, [5] functional solid supports, [6] etc.). [1] Various synthetic methods have been reported, but native chemical ligation (NCL) is one of the most frequently used techniques.…”

“…[1] Various synthetic methods have been reported, but native chemical ligation (NCL) is one of the most frequently used techniques. [4] In order to overcome this problem,s everal groups have developedt echniques for the removal of MPAA from reaction mixtures (liquid-liquide xtraction, [5] functional solid supports, [6] etc.). However, MPAA frequently coelutes with the ligatedp eptided uring HPLC purification,t hus hampering isolation of the ligated product.…”

“…However, MPAA frequently coelutes with the ligatedp eptided uring HPLC purification,t hus hampering isolation of the ligated product. [4] In order to overcome this problem,s everal groups have developedt echniques for the removal of MPAA from reaction mixtures (liquid-liquide xtraction, [5] functional solid supports, [6] etc.). [7] We recently reported that the ligation reaction of multi-Cys-containing peptides can also proceed in the absence of MPAA, so the ligation product can be readily isolated by HPLC purification.…”