The Effect of Selective D- or Nα-Methyl Arginine Substitution on the Activity of the Proline-Rich Antimicrobial Peptide, Chex1-Arg20

Abstract

In vivo pharmacokinetics studies have shown that the proline-rich antimicrobial peptide, A3-APO, which is a discontinuous dimer of the peptide, Chex1-Arg20, undergoes degradation to small fragments at positions Pro6-Arg7 and Val19-Arg20. With the aim of minimizing or abolishing this degradation, a series of Chex1-Arg20 analogs were prepared via Fmoc/tBu solid phase peptide synthesis with D-arginine or, in some cases, peptide backbone Nα-methylated arginine, substitution at these sites. All the peptides were tested for antibacterial activity against the Gram-negative bacterium Klebsiella pneumoniae. The resulting activity of position-7 substitution of Chex1-Arg20 analogs showed that arginine-7 is a crucial residue for maintaining activity against K. pneumoniae. However, arginine-20 substitution had a much less deleterious effect on the antibacterial activity of the peptide. Moreover, none of these peptides displayed any cytotoxicity to HEK and H-4-II-E mammalian cells. These results will aid the development of more effective and stable PrAMPs via judicious amino acid substitutions.

Photosynthetic and ascorbate-glutathione metabolism in the flag leaves as compared to spikes under drought stress of winter wheat (Triticum aestivum L.)

“…Water deficit occurred during the grain-filling phase, which has an adverse impact on wheat productivity and quality [ 2 , 8 , 10 ]. Wheat cultivars have adapted various drought tolerance mechanisms, which include formation of deeper roots, accumulation of higher biomass, exertion of better stomatal control over transpiration, enhancement of osmoprotective and antioxidant response [ 65 ], and importantly a better coordination of positive and negative regulation of gene expression [ 66 ]. It has been suggested that the ear photosynthesis of wheat can provide ranging from 20 to 40% of the total grain carbon, depending on genotype and growing conditions, for the photosynthesis in spike green parts (e.g.…”

Hydrocarbon Stapled Antimicrobial Peptides

“…Nowadays, many approaches have been proposed to improve serum stability and to increase antimicrobial activity [ 15 – 17 ], inter alia, d -amino acid substitution [ 18 ] or other non-ribosomal amino acid substitution [ 19 ], PEGylation [ 20 ], lipidization [ 21 ], and dimerization [ 22 ]. Another AMP design approach is peptide stapling.…”

HERV-W group evolutionary history in non-human primates: characterization of ERV-W orthologs in Catarrhini and related ERV groups in Platyrrhini

“…For instance, spread of ERVs during mammalian evolution dispersed a great number of interferon-inducible enhancers, thus shaping an effective regulatory network of innate immunity [ 25 ]. ERVs were also reported to influence the defence systems via RNA transcripts that can modulate host functions in a variety of mechanisms, among which RNA interference and innate immunity sensing of double-stranded RNA [ 10 , 26 ].…”