A Comparison of Linear and Cyclic Peptoid Oligomers as Potent Antimicrobial Agents

Abstract

We investigated the antimicrobial activities of N-substituted glycine "peptoid" oligomers incorporating cationic and hydrophobic side chains. Head-to-tail macrocyclization was employed to enhance antimicrobial activity. Both linear and cyclic peptoids, ranging from six to ten residues, demonstrate potent antimicrobial activity against Gram-positive and Gram-negative bacteria. These peptoids do not cause significant lysis of human erythrocytes, indicating selective antimicrobial activity. Conformational ordering established upon macrocyclization is generally associated with an enhanced capacity to inhibit bacterial cell growth. Moreover, increased hydrophobic surface area also plays a role in improving antimicrobial activity. We demonstrate the potency of a cyclic peptoid in exerting antimicrobial activity against clinical strains of S. aureus while deterring the emergence of antimicrobial resistance.

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

“…Peptoids have been shown to have promising activities against a wide range of Gram negative bacteria, Gram positive bacterial and fungal species that are comparable to many known antimicrobial peptides. [3][4][5][6][7][8][9] In our work, peptoids have been used as novel anti-infective compounds for treatment of the neglected tropical disease leishmaniasis. 5,10 Leishmaniasis is endemic in more than 80 countries worldwide and it is estimated that over 12 million people are infected globally.…”

The Development of Antimicrobial γ-Aapeptides

“…To circumvent those drawbacks, over last decade, non-natural peptidomimetics that mimic the globally amphipathic structures and mechanism of action of HDPs have been developed and investigated, such as β-peptides [17][18][19], peptoids [20][21][22][23][24], arylamide oligomers [25,26], β-turn mimetics [27,28] and others [29,30]. Recently, we developed a new class of peptidomimetics termed 'γ-AApeptides' [31,32].…”

Biomimetic peptoid oligomers as dual-action antifreeze agents

“…Peptoids can be synthesized efficiently on solid phase using a broad range of primary amines as synthons, thus greatly expanding their chemical diversity compared with natural polypeptides. Moreover, recent advances to induce peptoid conformational order (32)(33)(34) have enabled the discovery of biomimetic oligomers for materials (35), catalytic (36), and biomedical applications (37)(38)(39). Investigations of sequence-specific synthetic oligomers as modulators of crystallization (40)(41)(42), including the crystallization of ice, are sparse (43).…”