Chapter 6 - Polymer–drug linking through amide bonds: the chemistry and applications in drug delivery

Abstract

The amide group is referred to as a peptide bond when it is found in the main chain of a protein, and an amide bond (isopeptide) bond when it is located in the side chain of a protein, as in the amino acids asparagine and glutamine. The amide bond is the most fundamental functional group in many areas of chemistry, pharmacy, and bioengineering, such as chemical synthesis, drug discovery, polymers, and biochemistry. The amide functional group is important in the composition of biomolecules, including several therapeutically approved drugs. Bioisosterism is frequently employed in the rational modification of lead compounds to improve potency, selectivity, pharmacokinetic characteristics, reduce toxicity, and protect intellectual property by obtaining novel chemical space. The most common covalent connections for conjugating drugs to superparamagnetic iron oxide nanoparticles are amide bonds, which are created by reacting the drug with an amine. The reaction of an amine group with an N-hydroxysuccinimide (NHS)–activated carboxylic molecule to form an amide bond is a favored direct conjugation approach. By reacting a carboxylic molecule with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and NHS, a carboxylic molecule becomes an acyl amino ester.