The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggesting that local cohesive structures exist on the basis of β-sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. This information can be used to generate useful aggregate morphologies for improved biomedical function.
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http://dx.doi.org/10.1038/ncomms11561 | DOI Listing |
J Chem Inf Model
January 2025
Unit of Biophysics, Department of Biochemistry and Molecular Biology, Facultat de Medicina, Av. Can Domènech s/n, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Catalonia, Spain.
Cell-penetrating peptides (CPPs) can translocate into cells without inducing cytotoxicity. The internalization process implies several steps at different time scales ranging from microseconds to minutes. We combine adaptive Steered Molecular Dynamics (aSMD) with conventional Molecular Dynamics (cMD) to observe nonequilibrium and equilibrium states to study the early mechanisms of peptide-bilayer interaction leading to CPPs internalization.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with concern about inducing systemic immunotoxicity.
View Article and Find Full Text PDFChembiochem
January 2025
Sun Yat-Sen University, School of Pharmaceutical Sciences (Shenzhen), 132, East Outer Ring Road, Panyu, 518107, Shenzhen, CHINA.
In clinical practice, thymopentin (TP-5) is a commonly utilized immunomodulatory peptide drug. The relatively short half-life of TP-5, however, significantly limits its applicability in immunotherapy. Inspired by the structure of the TLR2 ligand lipopeptide Pam3CSK4, fatty acid-modified TP-5 peptides were designed and synthesized in this study.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Gause Institute of New Antibiotics, ul. Bolshaya Pirogovskaya, 11, Moscow 119021, Russia.
cyclic lipopeptides (CLP), part of the three main families-surfactins, iturins, and fengycins-are secondary metabolites with a unique chemical structure that includes both peptide and lipid components. Being amphiphilic compounds, CLPs exhibit antimicrobial activity in vitro, damaging the membranes of microorganisms. However, the concentrations of CLPs used in vitro are difficult to achieve in natural conditions.
View Article and Find Full Text PDFACS Appl Bio Mater
January 2025
School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, U.K.
A series of tripodal (three-arm) lysine-based peptides were designed and synthesized and their self-assembly properties in aqueous solution and antimicrobial activity were investigated. We compare the behaviors of homochiral tripodal peptides (KKY)K and a homologue containing the bulky aromatic fluorenylmethoxycarbonyl (Fmoc) group Fmoc-(KKY)K, and heterochiral analogues containing k (d-Lys), (kkY)K and Fmoc-(kkY)K. The molecular conformation and self-assembly in aqueous solutions were probed using various spectroscopic techniques, along with small-angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM).
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