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2000
Volume 32, Issue 11
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305
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Abstract

The natural horizon of the genetic code has expanded to incorporate amino acids, such as selenocysteine and pyrrolysine. Researchers have incorporated unnatural amino acids (UAAs) into target proteins, demonstrating increased protein functionality depending on their choice and target. The primary challenge in protein engineering is identifying novel antimicrobial short peptides effective against ESKAPE pathogens ( and ), which are categorized as multidrug-resistant (MDR). UAAs can be preferentially incorporated into short peptides to display therapeutic activity, potentially leading to next-generation targeted therapeutics. In purview of this, we have curated and summarized the applicability of genetic incorporations of UAAs in antimicrobial short peptides with a special emphasis on the importance of green synthesis. The approach affirmed a reduction in the toxicity of peptide drugs, making it biocompatible. This is an efficient protocol to develop novel antimicrobial short peptides catering to precision medications, particularly against MDR pathogens, as a sustainable pharmaceutical approach.

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2025-10-21
2026-03-09

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References

  1. AyyaduraiN. RameshkumarN. SoundrarajanN. EdwardrajaS. ParkH. LeeS. YooT.H. YoonS-G. Importance of expression system in the production of unnatural recombinant proteins in Escherichia coli.Biotechnol. Bioprocess Eng.; BBE200914225726510.1007/s12257‑009‑0009‑z
     [Google Scholar]
  2. WangX. YangX. WangQ. MengD. Unnatural amino acids: Promising implications for the development of new antimicrobial peptides.Crit. Rev. Microbiol.202349223125510.1080/1040841X.2022.2047008 35254957
     [Google Scholar]
  3. ChenX. HanJ. CaiX. WangS. Antimicrobial peptides: Sustainable application informed by evolutionary constraints.Biotechnol. Adv.20226010801210.1016/j.biotechadv.2022.108012 35752270
     [Google Scholar]
  4. AdhikariA. BhattaraiB.R. AryalA. ThapaN. KcP. MaharjanS. ChandaP.B. RegmiB.P. ParajuliN. Reprogramming natural proteins using unnatural amino acids.RSC Adv.20211160381263814510.1039/D1RA06322J
     [Google Scholar]
  5. DhanamS. RameshkumarN. KrishnanM. NagarajanK. Comparative assessment of bacteriocin and bacteriocin capped nanoparticles in mice model.Mater. Lett.202231313174010.1016/j.matlet.2022.131740
     [Google Scholar]
  6. HazamP.K. ChengC.C. LinW.C. HsiehC.Y. HsuP.H. ChenY.R. LiC.C. HsuehP.R. ChenJ.Y. Strategic modification of low-activity natural antimicrobial peptides confers antibacterial potential in vitro and in vivo.Eur. J. Med. Chem.202324911513110.1016/j.ejmech.2023.115131
     [Google Scholar]
  7. LuJ. XuH. XiaJ. MaJ. XuJ. LiY. FengJ. D- and unnatural amino acid substituted antimicrobial peptides with improved proteolytic resistance and their proteolytic degradation characteristics.Front. Microbiol.20201156303056303010.3389/fmicb.2020.563030 33281761
     [Google Scholar]
  8. WangC. GarlickS. ZlohM. Deep learning for novel antimicrobial peptide design.Biomolecules202111347110.3390/biom11030471
     [Google Scholar]
  9. RanbhorR. KumarA. TendulkarA. PatelK. RamakrishnanV. DuraniS. IDeAS: Automated design tool for hetero-chiral protein folds.Phys. Biol.201815606600510.1088/1478‑3975/aacdc3
     [Google Scholar]
  10. OikawaY. UzawaT. BerengerF. MinagawaN. YumotoA. TakakuH. TamuraR. ItoY. TsudaK. GPepT: A foundation language model for peptidomimetics incorporating noncanonical amino acids.ACS Med. Chem. Lett.20251681670167510.1021/acsmedchemlett.5c00375 40832546
     [Google Scholar]
  11. HudaP. HumphriesJ. FletcherN.L. HowardC.B. ThurechtK.J. BellC.A. Click-on antibody fragments for customisable targeted nanomedicines – site-specific tetrazine and azide functionalisation through non-canonical amino acid incorporation.Chem. Methods202442e20230003610.1002/cmtd.202300036
     [Google Scholar]
  12. ShandellM.A. TanZ. CornishV.W. Genetic code expansion: A brief history and perspective.Biochemistry202160463455346910.1021/acs.biochem.1c00286 34196546
     [Google Scholar]
  13. SinghS. KaulG. ShuklaM. AkhirA. TripathiS. GuptaA. BormonR. NairN.N. ChopraS. VermaS. Linear antimicrobial peptide, containing a diindolyl methane unnatural amino acid, potentiates gentamicin against methicillin-resistant Staphylococcus aureus.Drug Dev. Res.2025862e7007010.1002/ddr.70070 40025838
     [Google Scholar]
  14. SelvakumarE. RameshkumarN. LeeS.G. LeeS.J. ParkH.S. In vivo production of functional single-chain Fv fragment with an N-terminal-specific bio-orthogonal reactive group.ChemBioChem201011449850110.1002/cbic.200900685 20127780
     [Google Scholar]
  15. SampathG. ChenY-Y. RameshkumarN. KrishnanM. NagarajanK. ShyuD.J.H. Biologically synthesized silver nanoparticles and their diverse applications.Nanomaterials20221218312610.3390/nano12183126
     [Google Scholar]
  16. NgoP.H.T. IshidaS. BusogiB.B. DoH. LedesmaM.A. KarS. EllingtonA. Changes in coding and efficiency through modular modifications to a one pot PURE system for in vitro transcription and translation.ACS Synth. Biol.202312123771377710.1021/acssynbio.3c00461 38050859
     [Google Scholar]
  17. RubinS.J.S. QvitN. Backbone-cyclized peptides: A critical review.Curr. Top. Med. Chem.201818752655510.2174/1568026618666180518092333 29773062
     [Google Scholar]
  18. DubeyS.K. ParabS. DabholkarN. AgrawalM. SinghviG. AlexanderA. BapatR.A. KesharwaniP. Oral peptide delivery: Challenges and the way ahead.Drug Discov. Today202126493195010.1016/j.drudis.2021.01.001 33444788
     [Google Scholar]
  19. TalapkoJ. MeštrovićT. JuzbašićM. TomasM. ErićS. Horvat AleksijevićL. BekićS. SchwarzD. MatićS. NeubergM. ŠkrlecI. Antimicrobial peptides—mechanisms of action, antimicrobial effects and clinical applications.Antibiotics20221110141710.3390/antibiotics11101417
     [Google Scholar]
  20. ParkH. JinH. KimD. LeeJ. Cell-free systems: Ideal platforms for accelerating the discovery and production of peptide-based antibiotics.Int. J. Mol. Sci.20242516910910.3390/ijms25169109
     [Google Scholar]
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  • Article Type:     Editorial
Keyword(s): antimicrobial resistance; ESKAPE; precision medicine; short peptides; target proteins; UAAs

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