FROM STRUCTURE TO ACTIVITY: A COMPREHENSIVE REVIEW OF THE ANTIBACTERIAL PEPTIDE ANOPLIN
DOI:
https://doi.org/10.59957/jctm.v61.i4.2026.1Keywords:
Anoplin, antimicrobial peptides, structure - activity relationship, peptide modification.Abstract
Biologically active peptides are a promising alternative of the existing medical drugs used in the medicinal practice. Especially, antimicrobial peptides are such an alternative to conventional antibiotics considering the growing prevalence of antimicrobial resistance. Anoplin, a short decapeptide isolated from the venom of the solitary wasp Anoplius samariensis, has attracted attention due to the simple structure and membrane - targeting feature. This review summarizes current knowledge on the synthesis, structural characteristics, and biological activity of anoplin, with emphasis on structure - activity relationships and modification strategies. The activity of anoplin is closely related to its cationic and amphipathic nature. This allows interaction with bacterial membranes and leads to membrane disruption and cell death. Various modification approaches, including amino acid substitution, lipidation, and structural stabilization, have been applied to improve anoplin’s antimicrobial activity, selectivity, and stability. In addition, environmental factors such as ionic strength, pH, and proteolytic degradation significantly affect biological performance and bioavailability. Although anoplin shows relatively low susceptibility to resistance development, limitations related to stability and cytotoxicity is still a main disadvantage. Therefore, further optimization is required to enhance its therapeutic potential. Anoplin can serve as a useful model for the rational design of new antimicrobial peptides and peptide - based therapeutic agents.
References
W.H. Organization. Who statement on widespread antibiotic resistance. 2025 24 February 2026]; Available from: https://www.who.int/news/item/13-10-2025-who-warns-of-widespread-resistance-to-common-antibiotics-worldwide.
W.H. Organization, Global antibiotic resistance surveillance report 2025. 2025, Geneva. p. 114.
D.C. Nwobodo, M.C. Ugwu, C.O. Anie, M.T. Al-Ouqaili, J.C. Ikem, U.V. Chigozie,M. Saki, Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace, 2022.
M.E. Elshobary, N.K. Badawy, Y. Ashraf, A.A. Zatioun, H.H. Masriya, M.M. Ammar, N.A. Mohamed, S. Mourad, A.M. Assy, Combating antibiotic resistance: Mechanisms, multidrug-resistant pathogens, and novel therapeutic approaches: An updated review, Pharmaceuticals, 18, 3, 2025, 402.
F. Tavares-Carreon, K. De Anda-Mora, I.C. Rojas-Barrera, A. Andrade, Serratia marcescens antibiotic resistance mechanisms of an opportunistic pathogen: A literature review, PeerJ, 11, 2023, e14399.
M.E. Palmer, L.J. Andrews, T.C. Abbey, A.E. Dahlquist, E. Wenzler, The importance of pharmacokinetics and pharmacodynamics in antimicrobial drug development and their influence on the success of agents developed to combat resistant gram negative pathogens: A review, Frontiers in pharmacology, 13, 2022, 888079.
C.H. Wang, Y.H. Hsieh, Z.M. Powers, C.Y. Kao, Defeating antibiotic-resistant bacteria: Exploring alternative therapies for a post-antibiotic era, International journal of molecular sciences, 21, 3, 2020, 1061.
W.H. Organization, Global antimicrobial resistance and use surveillance system (glass) report: Antibiotic use data for 2022. 2025. p. 28.
C.H. Chen, T.K. Lu, Development and challenges of antimicrobial peptides for therapeutic applications, Antibiotics, 9, 1, 2020, 24.
M.S. Zharkova, D.S. Orlov, O.Y. Golubeva, O.B. Chakchir, I.E. Eliseev, T.M. Grinchuk, O.V. Shamova, Application of antimicrobial peptides of the innate immune system in combination with conventional antibiotics—a novel way to combat antibiotic resistance?, Frontiers in cellular and infection microbiology, 9, 2019, 128.
J.K. Boparai, P.K. Sharma, Mini review on antimicrobial peptides, sources, mechanism and recent applications, Protein and peptide letters, 27, 1, 2020, 4-16.
P. Gagat, M. Ostrówka, A. Duda-Madej, P. Mackiewicz, Enhancing antimicrobial peptide activity through modifications of charge, hydrophobicity, and structure, International Journal of Molecular Sciences, 25, 19, 2024, 10821.
A.H. Benfield, S.T. Henriques, Mode-of-action of antimicrobial peptides: Membrane disruption vs. Intracellular mechanisms, Frontiers in Medical Technology, 2, 2020, 610997.
Y. Utkin, Animal venoms and their components: Molecular mechanisms of action, Toxins, 13, 6, 2021, 415.
A.N. de Oliveira, A.M. Soares, S.L. Da Silva, Why to study peptides from venomous and poisonous animals?, International Journal of Peptide Research and Therapeutics, 29, 5, 2023, 76.
K. Konno, M. Hisada, R. Fontana, C.C. Lorenzi, H. Naoki, Y. Itagaki, A. Miwa, N. Kawai, Y. Nakata, T. Yasuhara, Anoplin, a novel antimicrobial peptide from the venom of the solitary wasp anoplius samariensis, Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology, 1550, 1, 2001, 70-80.
K. Chionis, D. Krikorian, A.I. Koukkou, M. Sakarellos‐Daitsiotis, E. Panou‐Pomonis, Synthesis and biological activity of lipophilic analogs of the cationic antimicrobial active peptide anoplin, Journal of Peptide Science, 22, 11-12, 2016, 731-736.
S. Gou, B. Li, X. Ouyang, Z. Ba, C. Zhong, T. Zhang, L. Chang, Y. Zhu, J. Zhang, N. Zhu, Novel broad-spectrum antimicrobial peptide derived from anoplin and its activity on bacterial pneumonia in mice, Journal of Medicinal Chemistry, 64, 15, 2021, 11247-11266.
M. Bobier, A. Joseph Villaraza,P. Mahal Sabido, Bismaleimidohexane-stapled anoplin analogs, in Journal of peptide science: Wiley 111 river st, hoboken 07030-5774, NJ USA, 2024.
J.K. Munk, L.E. Uggerhøj, T.J. Poulsen, N. Frimodt‐Møller, R. Wimmer, N.T. Nyberg, P.R. Hansen, Synthetic analogs of anoplin show improved antimicrobial activities, Journal of Peptide Science, 19, 11, 2013, 669-675.
Y. Wang, J. Chen, X. Zheng, X. Yang, P. Ma, Y. Cai, B. Zhang,Y. Chen, Design of novel analogues of short antimicrobial peptide anoplin with improved antimicrobial activity, Journal of Peptide Science, 20, 12, 2014, 945-951.
R.L. Salas, J.K.D. Garcia, A.C.R. Miranda, W.L. Rivera, R.B. Nellas, P.M.G. Sabido, Effects of truncation of the peptide chain on the secondary structure and bioactivities of palmitoylated anoplin, Peptides, 104, 2018, 7-14.
M.P. Dos Santos Cabrera, M. Arcisio‐Miranda, S.T. Broggio Costa, K. Konno, J.R. Ruggiero, J. Procopio, J. Ruggiero Neto, Study of the mechanism of action of anoplin, a helical antimicrobial decapeptide with ion channel‐like activity, and the role of the amidated c‐terminus, Journal of Peptide Science: An Official Publication of the European Peptide Society, 14, 6, 2008, 661-669.
S. Gou, B. Li, X. Ouyang, Z. Ba, C. Zhong, J. Ni, Tuning the activity of anoplin by dendrimerization of lysine and lipidation of the n-terminal, ACS omega, 6, 33, 2021, 21359-21367.
J. Jittikoon, Short native α-helical cationic antimicrobial peptides: Promising alternative antibiotics, The Thai Journal of Pharmaceutical Sciences, 39, 1, 2015, 1-9.
J.K. Munk, C. Ritz, F.P. Fliedner, N. Frimodt-Møller, P.R. Hansen, Novel method to identify the optimal antimicrobial peptide in a combination matrix, using anoplin as an example, Antimicrobial agents and chemotherapy, 58, 2, 2014, 1063-1070.
M. Zasloff, Antimicrobial peptides of multicellular organisms, nature, 415, 6870, 2002, 389-395.
B. Bechinger, K. Lohner, Detergent-like actions of linear amphipathic cationic antimicrobial peptides, Biochimica et Biophysica Acta (BBA)-Biomembranes, 1758, 9, 2006, 1529-1539.
W. Chan, P. White, Fmoc solid phase peptide synthesis: A practical approach. Vol. 222: OUP Oxford, 1999.
B. Liu, H. Huang, Z. Yang, B. Liu, S. Gou, C. Zhong, X. Han, Y. Zhang, J. Ni, R. Wang, Design of novel antimicrobial peptide dimer analogues with enhanced antimicrobial activity in vitro and in vivo by intermolecular triazole bridge strategy, Peptides, 88, 2017, 115-125.
J. Macyszyn, M. Burmistrz, A. Mieczkowski, M. Wojciechowska, J. Trylska, Conjugates of aminoglycosides with stapled peptides as a way to target antibiotic-resistant bacteria, ACS omega, 8, 21, 2023, 19047-19056.
D. Ifrah, X. Doisy, T.S. Ryge, P.R. Hansen, Structure‐activity relationship study of anoplin, Journal of Peptide Science: An Official Publication of the European Peptide Society, 11, 2, 2005, 113-121.
L.E. Uggerhøj, T.J. Poulsen, J.K. Munk, M. Fredborg, T.E. Sondergaard, N. Frimodt‐Moller, P.R. Hansen, R. Wimmer, Rational design of alpha‐helical antimicrobial peptides: Do's and don'ts, ChemBioChem, 16, 2, 2015, 242-253.
C. Zhong, Y. Zhu, N. Zhu, T. Liu, S. Gou, F. Zhang, J. Yao, J. Xie, J. Ni, Synthesis and anti-pseudomonal activity of new ß-ala modified analogues of the antimicrobial peptide anoplin, International Journal of Medical Microbiology, 310, 5, 2020, 151433.
K. Meinike, P. Hansen, Peptoid analogues of anoplin show antibacterial activity, Protein and Peptide Letters, 16, 9, 2009, 1006-1011.
K. Cruz Orozco, M.A. Ibarra Valencia, H. Barrios Camacho, G. Corzo Burguete, I. Arenas Sosa, Antimicrobial and antibiofilm activity of analogous synthetic peptides from anoplin, temporin, and aurein, International Journal of Peptide Research and Therapeutics, 31, 2, 2025, 25.
T. Liu, N. Zhu, C. Zhong, Y. Zhu, S. Gou, L. Chang, H. Bao, H. Liu, Y. Zhang, J. Ni, Effect of n-methylated and fatty acid conjugation on analogs of antimicrobial peptide anoplin, European Journal of Pharmaceutical Sciences, 152, 2020, 105453.
J.C. Slootweg, T.B. van Schaik, H.L.C.Q. van Ufford, E. Breukink, R.M. Liskamp, D.T. Rijkers, Improving the biological activity of the antimicrobial peptide anoplin by membrane anchoring through a lipophilic amino acid derivative, Bioorganic & medicinal chemistry letters, 23, 13, 2013, 3749-3752.
C. Zhong, N. Zhu, Y. Zhu, T. Liu, S. Gou, J. Xie, J. Yao, J. Ni, Antimicrobial peptides conjugated with fatty acids on the side chain of d-amino acid promises antimicrobial potency against multidrug-resistant bacteria, European Journal of Pharmaceutical Sciences, 141, 2020, 105123.
C. Zhong, T. Liu, S. Gou, Y. He, N. Zhu, Y. Zhu, L. Wang, H. Liu, Y. Zhang, J. Yao, Design and synthesis of new n-terminal fatty acid modified-antimicrobial peptide analogues with potent in vitro biological activity, European Journal of Medicinal Chemistry, 182, 2019, 111636.
M. Kai, W. Zhang, H. Xie, L. Liu, S. Huang, X. Li, Z. Zhang, Y. Liu, B. Zhang, J. Song, Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides, Chinese Chemical Letters, 29, 7, 2018, 1163-1166.
M. Wojciechowska, J. Miszkiewicz, J. Trylska, Conformational changes of anoplin, w-mreb1–9, and (kff) 3k peptides near the membranes, International journal of molecular sciences, 21, 24, 2020, 9672.
S.S. Ranade, R. Ramalingam, Hydrogen bonds in anoplin peptides aid in identification of a structurally stable therapeutic drug scaffold, Journal of Molecular Modeling, 26, 6, 2020, 155.
C. Chamorro, M.A. Boerman, C.J. Arnusch, E. Breukink, R.J. Pieters, Enhancing membrane disruption by targeting and multivalent presentation of antimicrobial peptides, Biochimica et Biophysica Acta (BBA)-Biomembranes, 1818, 9, 2012, 2171-2174.
P. Sahariah ,K.K. Sørensen, M.Á. Hjálmarsdóttir, Ó.E. Sigurjónsson, K.J. Jensen, M. Másson, M.B. Thygesen, Antimicrobial peptide shows enhanced activity and reduced toxicity upon grafting to chitosan polymers, Chemical communications, 51, 58, 2015, 11611-11614.
C. Zhong, J. Zou, W. Mao, P. Yang, J. Zhang, S. Gou, Y. Zhang, H. Liu,J. Ni, Structure modification of anoplin for fighting resistant bacteria, European Journal of Medicinal Chemistry, 268, 2024, 116276.
Q.Y. Zhang, Z.B. Yan, Y.M. Meng, X.Y. Hong, G. Shao, J.J. Ma, X.R. Cheng, J. Liu, J. Kang, C.Y. Fu, Antimicrobial peptides: Mechanism of action, activity and clinical potential, Military Medical Research, 8, 1, 2021, 48.
Y. Shai, Mode of action of membrane active antimicrobial peptides, Peptide Science: Original Research on Biomolecules, 66, 4, 2002, 236-248.
S. Guha, J. Ghimire, E. Wu, W.C. Wimley, Mechanistic landscape of membrane-permeabilizing peptides, Chemical reviews, 119, 9, 2019, 6040-6085.
H. Syed, M. Tauseef, Z. Ahmad, A connection between antimicrobial properties of venom peptides and microbial atp synthase, International journal of biological macromolecules, 119, 2018, 23-31.
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