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Peptides have attracted great interest as platforms for the design of nanocomposite hydrogels due to their distinct bioactivity, biofunctionality and biocompatibility. Previously, we have reported on a family of peptides that self-assembled to form stabilised three-dimensional hydrogel networks, displaying potent antimicrobial activity. In this paper, we report on the use of these hydrogelator sequences and their analogues as stabilisers and growth controllers to synthesise anisotropic gold nanoparticles (AuNPs) of different sizes and shapes. In particular, hollow spherical nanoparticles were obtained for HG2.81-AuNPs, whereas hexagonal nanoparticles were observed for TOH_1N-AuNPs and PentaOH-AuNPs in their respective hydrogel networks. The PentaOH-AuNPs' hydrogel exhibited excellent results with high antimicrobial potency against Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 and negligible cytotoxicity. On the other hand, TOH_1N-AuNPs showed no antibacterial activity and no cytotoxicity, demonstrating the versatility of these peptides. This work gives credence towards the development of these materials towards further applications such as in tissue culture technology and wound dressing materials., (© 2024 The Author(s). Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)

Cheap artificial light harvesting systems, which competently harvest solar energy and promote efficient energy transfer, are highly sought after in the renewable sector. We report the synthesis of self-assembled peptide-porphyrin fibers (SJ 6) fabricated with iron(III) oxide (Fe 3 O 4 ) nanoparticles as feasible electron acceptors. Charge-complementarity between the negatively charged peptide (20E) and the protonated Zn-tetraphenyl porphyrin (ZnTPyP) led to an ordered assembly of the ZnTPyP molecules, enabling efficient light harvesting. X-ray diffraction data indicates a more ordered structure in SJ 6 compared to 20E and ZnTPyP. The incorporation of Fe 3 O 4 nanoparticles into SJ 6 showed significant fluorescence quenching, indicating efficient electron flow from the donor to the acceptor. The SJ 6-nFe 3 O 4 system performed the light reaction of photosynthesis as confirmed by the reduction of 1 mM NAD + to 0.180 mM NADH upon exposure to visible light (Xe lamp λ > 420 nm) for 1 h. The photochemical regeneration of NADH using the SJ 6-nFe 3 O 4 system was coupled to glutamate dehydrogenase-catalyzed conversion of α-ketoglutarate to L-glutamate. These results confirm the successful synthesis of an artificial light harvesting peptide-porphyrin system with Fe 3 O 4 nanoparticles as promising low-cost electron separators., (© 2022 European Peptide Society and John Wiley & Sons Ltd.)

The effect on secondary structure and antimicrobial activity of introducing different cyclic constraints in linear β-hairpin antimicrobial peptides has been investigated with the intention of generating cyclic β sheets as promising antimicrobials with improved therapeutic potential. The linear peptides were cyclized head to tail either directly or after the addition of either a second turn motif or a disulfide bridge. The propensity of these peptides to adopt a cyclic β-sheet structure has been correlated to their antibacterial activity. All cyclic peptides showed enhanced activity, compared with their linear counterparts against methicillin-resistant Staphylococcus aureus. Scanning electron microscopy and transmission electron microscopy studies showed that this family kills bacteria through membrane lysis. The peptide that showed the best efficacy against all strains (exhibiting nanomolar activity), while retaining low haemolysis, bears two symmetrical, homochiral d-phe-2-Abz-d-ala turns and adopted a flexible structure. Its twin peptide that bears heterochiral turns (one with d-ala and one with L-Ala) showed reduced antibacterial activity and higher percentage of haemolysis. Circular dichroism and nuclear magnetic resonance spectroscopy indicate that heterochirality in the two turns leads to oligomerization of the peptide at higher concentrations, stabilizing the β-sheet secondary structure. More rigid secondary structure is associated with lower activity against bacteria and loss of selectivity., (© 2020 European Peptide Society and John Wiley & Sons, Ltd.)

Antibiotic resistance is a major public health problem globally. Particularly concerning amongst drug-resistant human pathogens is Mycobacterium tuberculosis that causes the deadly infectious tuberculosis (TB) disease. Significant issues associated with current treatment options for drug-resistant TB and the high rate of mortality from the disease makes the development of novel treatment options against this pathogen an urgent need. Antimicrobial peptides are part of innate immunity in all forms of life and could provide a potential solution against drug-resistant TB. This review is a critical analysis of antimicrobial peptides that are reported to be active against the M tuberculosis complex exclusively. However, activity on non-TB strains such as Mycobacterium avium and Mycobacterium intracellulare, whenever available, have been included at appropriate sections for these anti-TB peptides. Natural and synthetic antimicrobial peptides of diverse sequences, along with their chemical structures, are presented, discussed, and correlated to their observed antimycobacterial activities. Critical analyses of the structure allied to the anti-mycobacterial activity have allowed us to draw important conclusions and ideas for research and development on these promising molecules to realise their full potential. Even though the review is focussed on peptides, we have briefly summarised the structures and potency of the various small molecule drugs that are available and under development, for TB treatment., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Three linear peptides incorporating d-Phe-2-Abz as the turn motif are reported. Peptide 1, a hydrophobic β-hairpin, served as a proof of principle for the design strategy with both NMR and CD spectra strongly suggesting a β-hairpin conformation. Peptides 2 and 3, designed as amphipathic antimicrobials, exhibited broad spectrum antimicrobial activity, with potency in the nanomolar range against Staphylococcus aureus. Both compounds possess a high degree of selectivity, proving non-haemolytic at concentrations 500 to 800 times higher than their respective minimal inhibitory concentrations (MICs) against S. aureus. Peptide 2 induced cell membrane and cell wall disintegration in both S. aureus and Pseudomonas aeruginosa as observed by transmission electron microscopy. Peptide 2 also demonstrated moderate antifungal activity against Candida albicans with an MIC of 50 μM. Synergism was observed with sub-MIC levels of amphotericin B (AmB), leading to nanomolar MICs against C. albicans for peptide 2. Based on circular dichroism spectra, both peptides 2 and 3 appear to exist as a mixture of conformers with the β-hairpin as a minor conformer in aqueous solution, and a slight increase in hairpin population in 50% trifluoroethanol, which was more pronounced for peptide 3. NMR spectra of peptide 2 in a 1:1 CD 3 CN/H 2 O mixture and 30 mM deuterated sodium dodecyl sulfate showed evidence of an extended backbone conformation of the β-strand residues. However, inter-strand rotating frame Overhauser effects (ROE) could not be detected and a loosely defined divergent hairpin structure resulted from ROE structure calculation in CD 3 CN/H 2 O. The loosely defined hairpin conformation is most likely a result of the electrostatic repulsions between cationic strand residues which also probably contribute towards maintaining low haemolytic activity., (Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.)

Intrinsically disordered proteins that exist as unordered monomeric structures in aqueous solution at pH 7 but fold into four-helix bundles upon binding to recognized polypeptide targets have been designed. NMR and CD spectra of the monomeric polypeptides show the hallmarks of unordered structures, whereas in the bound state they are highly helical. Analytical ultracentrifugation data shows that the polypeptides bind to their targets to form exclusively heterodimers at neutral pH. To demonstrate the relationship between binding, folding, and function, a catalytic site for ester hydrolysis was introduced into an unordered and largely inactive monomer, but that was structured and catalytically active in the presence of a specific polypeptide target. Electrostatic interactions between surface-exposed residues inhibited the binding and folding of the monomers at pH 7. Charge-charge repulsion between ionizable amino acids was thus found to be sufficient to disrupt binding between polypeptide chains despite their inherent propensities for structure formation and may be involved in the folding and function of inherently disordered proteins in biology., (Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.)

The solution conformation of a designed tetradecapeptide Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (Dpg-14) containing two di-n-propyl glycine (Dpg) residues has been investigated by (1)H NMR and circular dichroism in organic solvents. The peptide aggregates formed at a concentration of 3 mM in the apolar solvent CDCl(3) were broken by the addition of 12% v/v of the more polar solvent DMSO-d(6). Successive N(i)H <--> N(i+1)H NOEs observed over the entire length of the sequence in this solvent mixture together with the observation of several characteristic medium-range NOEs support a major population of continuous helical conformations for Dpg-14. Majority of the observed coupling constants (3)JNHC(alpha)H) also support phi values in the helical conformation. Circular dichroism spectra recorded in methanol and propan-2-ol give further support in favor of helical conformation for Dpg-14 and the stability of the helix at higher temperature., (Copyright (c) 2010 European Peptide Society and John Wiley & Sons, Ltd.)