Expanding the Landscape of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment in Nature, Implications for Peptide Design and Therapeutic Potential

Abstract

Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (>25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 peptides, 724 rich AMPs were identified. Rich AMPs are more common in animals and bacteria than in plants. In different animal classes, a unique set of rich AMPs is deployed. While histidine, proline, and arginine-rich AMPs are abundant in mammals, alanine, glycine, and leucine-rich AMPs are common in amphibians. Ten amino acids (Ala, Cys, Gly, His, Ile, Lys, Leu, Pro, Arg, and Val) are frequently observed in rich AMPs, seven (Asp, Glu, Phe, Ser, Thr, Trp, and Tyr) are occasionally observed, and three (Met, Asn, and Gln) were not yet found. Leucine is much more frequent in forming rich AMPs than either valine or isoleucine. To date, no natural AMPs are simultaneously rich in leucine and lysine, while proline, tryptophan, and cysteine-rich peptides can simultaneously be rich in arginine. These findings can be utilized to guide peptide design. Since multiple candidates are potent against antibiotic-resistant bacteria, rich AMPs stand out as promising future antibiotics.

In Silico Design and Synthesis of Antifungal Peptides Guided by Quantitative Antifungal Activity

“…As a preliminary overview of the peptides to be designed, the physicochemical properties, including amino acid composition, sequence length, and AFI distribution, were calculated, as depicted in Figure . The amino acid composition (Figure A) revealed a predominance of arginine, leucine, and lysine, which is consistent with previous reports highlighting the prevalence of positively charged amino acids in AFPs. − Figure B illustrates the distributions of sequence length and AFI, with most sequence lengths falling within the ranges of 20–25 and 35–40 residues. The majority of AFI is in the range of 3.00–5.00 μM, and only four sequences possess AFI smaller than 3.00 μM.…”

The antimicrobial peptide database is 20 years old: Recent developments and future directions

“…SAAP fraction 3, a surfactant‐associated anionic peptide, consists of a string of aspartic acids (Brogden et al, 1996), while shepherins comprised primarily glycine and histidine residues (Park et al, 2000). These are amino acid‐rich peptides where at least one amino acid is greater than 25% in the sequence (Decker et al, 2022). Only two cyclic peptides, baceridin, and lugdunin, are entirely hydrophobic (100%; Niggemann et al, 2014; Zipperer et al, 2016).…”

“…Finally, the UCBB peptides contain a chemical bond that connects the N and C‐termini of the peptide. In addition, the APD provides a platform for understanding the design principles of natural AMPs (Decker et al, 2022; Lakshmaiah Narayana et al, 2020; Wang, 2020a; Wang, 2020b). Peptides with different activities, structures, and mechanisms of action can all be grouped and analyzed.…”

Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

“…The number of non-polar amino acids with large side-chains seem to have a key role in SCHAMPs activity. Leucine, phenylalanine, tyrosine, and tryptophan are found in many AMPs 85 . In the case of Temporin-L, when substituting both Phe3 and Phe5 with leucines, the modified Temporin-L has no activity against E. coli and P. aeruginosa 86 .…”