An Overview of the Synthesis of Highly Versatile N-Hydroxysuccinimide Esters

Abstract

N-Hydroxysuccinimide esters (NHS-esters) are important and widely used tools in various areas of chemistry including peptide synthesis, bioconjugate chemistry, functionalized materials and polymers. The usual strategy employed to prepare these active esters generally relies on the coupling reaction with a carboxylic acid and N-hydroxysuccinimide in the presence of a coupling agent. However, more recently, many other efficient strategies have emerged in the literature. This short review covers the literature devoted to the preparation of these valuable N-hydroxysuccinimide esters. 1 Introduction 2 N-Hydroxysuccinimide Coupling Reaction with Activated Carboxylic Acids 3 Carboxylic Acid Coupling Reaction with Activated N-Hydroxysuccinimide 4 Alcohol and Aldehyde Coupling Reaction with N-Hydroxysuccinimide under Oxidizing Conditions 5 Carbonylative Cross-Coupling Reaction 6 Conclusion

Nanoporous Carbon Immunosensor for Highly Accurate and Sensitive Clinical Detection of Glial Fibrillary Acidic Protein in Traumatic Brain Injury, Stroke, and Spinal Cord Injury

“…Dry and stable activated NHS ester reacts with lysine residues in the GFAP antibody to form the amide bond. 57,58 EDC−NHS mediated crosslinking on the modified electrodes, which enables GFAP-antibody binding to the electrode surface.…”

“…The electrodes were then washed with PBS, followed by introducing 60 mM EDC and 80 mM NHS (1:1) to the electrode for 4 h. NHS coupled with EDC forms NHS ester with the amine group on the electrode’s surface. Dry and stable activated NHS ester reacts with lysine residues in the GFAP antibody to form the amide bond. , EDC–NHS mediated crosslinking on the modified electrodes, which enables GFAP-antibody binding to the electrode surface.…”

Versatile Platinum(IV) Prodrugs of Naproxen and Acemetacin as Chemo-Anti-Inflammatory Agents

“…The NHS esters of NPX and ACE were prepared using previously established protocols without modifications (see Supplementary Materials) [52][53][54].…”

ACTIVE‐BAPO – A Versatile Transfer Agent for Photoactive Bis(acyl)phosphane Oxide Units

“…One of the most versatile techniques for functionalizing biomolecules such as amino acids and peptides involves the use of chemical groups that react selectively with primary amines. For this purpose, NHS esters have proven the most popular amine‐specific functional groups, employed not only for ligations to peptides and proteins but also to dendrimers with terminal NH 2 , such as poly(propylenimine) dendrimers (DAB‐dendrimer) and poly(amidoamine) dendrimers (PAMAM) [11–22] . The reactions are usually performed in aqueous media under mild conditions upon formation of the ligate with an amide bond and giving N ‐hydroxy succinimide, NHS, as the only by‐product (Scheme 1c).…”

“…For this purpose, NHS esters have proven the most popular aminespecific functional groups, employed not only for ligations to peptides and proteins but also to dendrimers with terminal NH 2 , such as poly(propylenimine) dendrimers (DAB-dendrimer) and poly(amidoamine) dendrimers (PAMAM). [11][12][13][14][15][16][17][18][19][20][21][22] The reactions are usually performed in aqueous media under mild conditions upon formation of the ligate with an amide bond and giving Nhydroxy succinimide, NHS, as the only by-product (Scheme 1c). This preparative method is very convenient for water-soluble substrates and several ligation kits with activated esters are commercially available.…”