Protecting groups and their essential role in peptide API synthesis

Los grupos protectores y su papel esencial en la síntesis de APIs peptídicos

Proteins, the backbone of biological systems, orchestrate a multitude of essential functions within the human body. Their intricate structures and diverse roles have driven extensive research efforts aimed at understanding their significance in health and disease. As a result, protein research has flourished, leading to a deepened understanding of their functions.

This enhanced understanding of proteins has sparked a revolution in pharmaceutical research. Peptides, fragments derived from proteins or small aminoacidic sequences, have emerged as promising therapeutic agents due to their specificity, efficacy, and favorable safety profiles. Consequently, an increasing number of active pharmaceutical ingredients (APIs) are peptides, such as insulin, semaglutide, and abaloparatide.

Peptide APIs, being organic molecules, are synthesized through multistep organic synthesis processes, where precise modifications are essential to their efficacy and safety. Protecting groups play a crucial role in this organic synthesis, shielding reactive functional groups to allow subsequent steps to proceed without interference.

Among the array of protecting groups, the tert-butyloxycarbonyl (BOC) group and the Fluorenylmethyloxycarbonyl (Fmoc) group stand out in peptide synthesis. By transforming amines into carbamates, these groups protect the N-termini of amino acids, as well as the amine groups found in some of the variable side chains, from unwanted reactions with nucleophiles and bases.

In particular, BOC protection typically occurs in solvents like water/THF, THF, or acetonitrile, often with the presence of a base such as NaOH. Deprotection, on the other hand, involves carbamate hydrolysis under acidic and preferably anhydrous conditions, often using HCl in an organic solvent like ethanol or ethyl acetate. The use of scavengers is also recommended during deprotection to mitigate the risk of undesired reactions.

At GRIT, we specialize in providing solutions tailored to the needs of API synthesis. Our expertise in dissolving hazardous gases like HCl into organic solvents enables us to produce Gas-To-Liquid (GTL) solutions, which serve as excellent allies in BOC deprotection, as well as multiple other stages of organic synthesis processes. Moreover, our support extends seamlessly to peptide synthesis, facilitating the production of peptide APIs, an essential activity for modern pharmacotherapy.

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