Peptoids (N-substituted polyglycines) represent a class of bioinspired oligomers that have unique physical and structural properties. Here we report the construction of "extended peptoids" based on aromatic building blocks, in which the N-alkylaminoacetyl group of the peptoid backbone has been replaced by an N-alkylaminomethylbenzoyl spacer. Both meta-and para-bromomethylbenzoic acids were synthesized, providing access to a new class of peptoids. Further, inclusion of hydrophilic side chains confers water solubility to these compounds, showing that, like simple peptoids, extended peptoids add an extra dimension to synthetic polyamide oligomers with potential application in a variety of biological contexts.
Keywordspeptoids; N-alkyl glycines; oligomers; bioinspired polymers Peptoids 1 (N-substituted glycines) represent an interesting class of biomimetic oligomers that are structurally related to peptides but have different biological 2,3 and conformational 4-6 properties. The submonomer method of peptoid synthesis introduced by Zuckermann, et al., 7 allows for considerable diversity to be incorporated into the construction of peptoid libraries due to the large number of commercially available primary amines. The submonomer method has been applied extensively in the creation of peptoid libraries 8-12 , and it has shown great versatility in incorporating a diverse set of amines 13, 14 and hydrazines 15 . The peptoid scaffold has been further modified to create ureapeptoids 16, 17 and incorporate a variety of chemoselective functionalities 18 . The bulk of these studies, however, have preserved the haloacetic acid component while focusing on variations in the nucleophilic displacement step. Here we report the solid-phase synthesis of a new class of peptoid-inspired biomimetics in which the haloacetic acid groups are replaced by either meta-or para-halomethylbenzoic acids ( Figure 1b). These extended peptoids add further geometric diversity to oligomers based on the peptoid concept.The synthesis of meta-extended peptoids is shown in Scheme 1. m-and p-bromomethylbenzoic acids were readily synthesized by bromination of the corresponding toluic acids 19 . All of the extended peptoids described here were synthesized on Wang resin (100-200 mesh, 1.1 mmole/ g) 2 . The first bromomethylbenzoic acid submonomer was coupled to the resin with Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript diisopropylcarbodiimide (DIC) and 4-dimethylaminopyridine (DMAP) in dry DCM over one hour at room te...