Enlarging the chemical space of anti-leishmanials: a structure–activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis

Abstract

Peptoids with promising activity against intracellularLeishmania mexicanaamastigotes have been identified.

Peptoid Efficacy against Polymicrobial Biofilms Determined by Using Propidium Monoazide‐Modified Quantitative PCR

“…The peptoid library contained peptoids of three different lengths: six‐, nine‐ and twelve‐residue peptoid analogues. In agreement with previous studies, the longest (twelve‐residue) peptoids tended to be most efficacious. They were more active against C. albicans than nine‐residue peptoids, and the six‐residue sequences were mostly inactive (compare 7 (dodecamer), 8 (nonamer) and 9 (hexamer)).…”

“…The sequences were designed around an NxNyNy subunit (Table ), repeated two, three or four times (six‐, nine‐ and twelve‐residue peptoids respectively), where Nx is a positively charged lysine‐type amine with various side‐chain lengths ( N ah N ‐(6‐aminohexyl)glycine, N Lys N ‐(4‐aminobutyl)glycine and N ae N ‐(2‐aminoethyl)glycine), and Ny is either the chiral aromatic building block N spe N ‐( S ‐phenylethyl)glycine or the achiral N phe N ‐benzylglycine. Peptoids were synthesised with a repeat unit of three residues in order to induce an amphipathic structure; the bulky N phe and N spe monomers were included as these have been reported to encourage a helical structure that can lead to an improved antimicrobial activity . The 18 peptoids are classified into three families (peptoids 1 – 6 , 7 – 12 and 13 – 18 ) based on their positively charged building blocks ( N ah, N Lys or N ae).…”

“…Peptoids were synthesised with ar epeatu nit of three residues in order to inducea na mphipathic structure;t he bulky Nphe and Nspe monomers were included as these have been reportedt oe ncourage ah elical structure that can lead to an improved antimicrobial activity. [28][29][30][31] The 18 peptoids are classified into three families (peptoids 1-6, 7-12 and 13-18)b ased on their positively charged building blocks (Nah, NLyso rNae). All peptoids were synthesised manually on resin by the sub-monomer method [32] on as haker platform at room temperature (15 min acylation steps and1 5min displacement steps).…”

Synthesis of Antibacterial Nisin–Peptoid Hybrids Using Click Methodology

“…A strategy that is more commonly being utilized to stabilize peptide-based therapeutics is the synthesis of stable peptidomimetics such as peptoids ( N -substituted glycines) ( Figure 2 ) [ 18 , 19 , 20 ]. Peptoids have shown activity as antibacterial [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], antifungal [ 29 , 30 , 31 ] and antiparasitic [ 32 , 33 , 34 , 35 ] compounds and most importantly they display increased resistance to protease action compared to α-peptides [ 31 , 36 ]. In particular, peptoids have demonstrated antibacterial properties against a range of clinically relevant Gram negative and Gram positive bacteria, with activities that equal or surpass those achieved by many antimicrobial peptides (AMPs) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

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

“…[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. 11 The disease is caused by protozoan parasites that are transmitted by the bite of a sandfly.…”