Peptoid SynthesisPharmaceutical InformationUpdated on Jul 30, 2019 View more like this | Visit SHIRLEY, NY | Contact Cathy Miller |
Synthesis of peptoid
• Solid-Phase Synthesis
The first oligopeptoids reported were synthesized by solid-phase synthesis, for which a set of Fmoc-protected peptoid monomers was made. There are several advantages to this method, but the extensive synthetic effort required to prepare a suitable set of chemically diverse monomers is a significant disadvantage of this approach. Additionally, the secondary N-terminal amine in peptoid oligomers is more sterically hindered than the primary amine of an amino acid, which slows coupling reactions.
• Sub-monomer Solid-Phase Method
A major breakthrough came in 1992 when a much more efficient method of peptoid synthesis was invented. In this method, each N-substituted glycine (NSG) monomer is assembled from two readily available “sub-monomers” in the course of extending the NSG oligomer, this method is known as the sub-monomer method, in which each cycle of monomer addition consists of two steps, an acylation step and a nucleophilic displacement step.
• Side Reactions
There are a few competing side reactions that are unique to the synthesis of peptoid oligomers. For example, peptoid dimer synthesis often leads to formation of the cyclic diketopiperazines instead of the linear molecule. Sub-monomer whose side chains bear a nucleophile three of four atoms from the amino nitrogen, are also prone to cyclization after bromoacetylation.
• Solid-Phase Synthesis
The first oligopeptoids reported were synthesized by solid-phase synthesis, for which a set of Fmoc-protected peptoid monomers was made. There are several advantages to this method, but the extensive synthetic effort required to prepare a suitable set of chemically diverse monomers is a significant disadvantage of this approach. Additionally, the secondary N-terminal amine in peptoid oligomers is more sterically hindered than the primary amine of an amino acid, which slows coupling reactions.
• Sub-monomer Solid-Phase Method
A major breakthrough came in 1992 when a much more efficient method of peptoid synthesis was invented. In this method, each N-substituted glycine (NSG) monomer is assembled from two readily available “sub-monomers” in the course of extending the NSG oligomer, this method is known as the sub-monomer method, in which each cycle of monomer addition consists of two steps, an acylation step and a nucleophilic displacement step.
• Side Reactions
There are a few competing side reactions that are unique to the synthesis of peptoid oligomers. For example, peptoid dimer synthesis often leads to formation of the cyclic diketopiperazines instead of the linear molecule. Sub-monomer whose side chains bear a nucleophile three of four atoms from the amino nitrogen, are also prone to cyclization after bromoacetylation.
