Funded by the German Federal Foreign Office

German Federal Foreign Office
DAAD Global Centres
Charité
Martin Luther Universität Halle-Wittenberg
Leibniz Institute of Plant Biochemistry
National Autonomous University of Mexico
University of Havana
Exploration of the Tertiary Amide Chemical Space of Dolastatin 15 Analogs Reveals New Insights into the Structure–Anticancer Activity Relationship

Exploration of the Tertiary Amide Chemical Space of Dolastatin 15 Analogs Reveals New Insights into the Structure–Anticancer Activity Relationship

by | Oct 13, 2025 | Bioactive Compounds, Publications

Dolastatins are a class of naturally occurring antimitotic peptides that have inspired the development of some of the most active and widely used anticancer agents. Here, we report on the development of synthetic methodologies for the preparation of parallel libraries of small peptides inspired by dolastatin 15 and itsanalogs cemadotin and tasidotin. The approaches rely on the use of either one or multiple Ugi-multicomponent reactions to generate amide N-substituted dolastatin-like skeletons, which allow the exploration of tertiary amide chemical spaces that have not been assessed previously. Evaluation of the anticancer activity in a variety of cancer cells showed that introducing a tertiary amide at the C-terminal fragment or by replacement of a proline residue does not lead to an increment in the anti-proliferative activity. The microtubule-disrupting capacity of the new dolastatin analogs was studied and compared with other potent antimitotic agents, thereby shedding light on mechanistic details of their anti-proliferative activity.

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Viral Symmetries

Viral Symmetries

by | Aug 29, 2025 | Events, News, Upcoming

Viral Symmetries is a bioart exhibition that transforms the invisible world of viruses into a visual and sensory experience. The artworks are based on real structural data of viral capsids—nature’s geometric designs that allow viruses to persist and interact with their hosts.

Through colors, shapes, 3D visualizations, and original music, the exhibition highlights the beauty and complexity of viral symmetries, from icosahedrons to spirals, patterns deeply connected with both molecular biology and the ancient idea of “sacred geometry”.

 

The exhibition features five viruses that researchers at the Charité Institute of Virology frequently study in the laboratory, making it directly relevant to GLACIER’s mission of advancing interdisciplinary perspectives on health. Created by Dr. Jorge Arias, visiting scientist from Costa Rica, with mapping by Carlos Infante, Viral Symmetries invites us to look at viruses not only as agents of disease, but also as expressions of nature’s underlying harmony.

Currently on display at the Berlin Institute of Health.

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Pore-forming peptide C14R exhibits potent antifungal activity against clinical isolates of Candida albicans and Candida auris

Pore-forming peptide C14R exhibits potent antifungal activity against clinical isolates of Candida albicans and Candida auris

by | Jul 4, 2025 | Bioactive Compounds, Publications

Introduction: Invasive candidiasis is a global public health problem as it poses a significant threat in hospital-settings. The aim of this study was to evaluate C14R, an analog derived from peptide BP100, as a potential antimicrobial peptide against the prevalent opportunistic yeast Candida albicans and the emergent multidrug-resistant yeast Candida auris.

Methods: Antifungal susceptibility testing of C14R against 99 C. albicans and 105 C. auris clinical isolates from Colombia, was determined by broth microdilution. Fluconazole was used as a control antifungal. The synergy between C14R and fluconazole was assessed in resistant isolates. Assays against fungal biofilm and growth curves were also carried out. Morphological alterations of yeast cell surface were evaluated by scanning electron microscopy. A permeability assay verified the pore-forming ability of C14R.

Results: C. albicans and C. auris isolates had a geometric mean MIC against C14R of 4.42 µg/ml and 5.34 µg/ml, respectively. Notably, none of the isolates of any species exhibited growth at the highest evaluated peptide concentration (200 µg/ml). Synergistic effects were observed when combining the peptide and fluconazole. C14R affects biofilm and growth of C. albicans and C. auris. Cell membrane disruptions were observed in both species after treatment with the peptide. It was confirmed that C14R form pores in C. albicans’ membrane.

Discussion: C14R has a potent antifungal activity against a large set of clinical isolates of both C. albicans and C. auris, showing its capacity to disrupt Candida membranes. This antifungal activity remains consistent across isolates regardless of their clinical source. Furthermore, the absence of correlation between MICs to C14R and resistance to fluconazole indicates the peptide’s potential effectiveness against fluconazole-resistant strains. Our results suggest the potential of C14R, a pore-forming peptide, as a treatment option for fungal infections, such as invasive candidiasis, including fluconazole and amphotericin B -resistant strains.

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Multicomponent Functionalization of the Octreotide Peptide Macrocyclic Scaffold

Multicomponent Functionalization of the Octreotide Peptide Macrocyclic Scaffold

by | Jul 4, 2025 | Bioactive Compounds, Publications

The replacement of the disulfide bridge by other types of side chain linkages has been a continuous endeavor in the development of cyclic peptide drugs with improved metabolic stability. Octreotide is a potent and selective somatostatin analog that has been used as an anticancer agent, in radiolabeled conjugates for the localization of tumors and as targeting moiety in peptide-drug conjugates. Here, we describe an on-resin methodology based on a multicomponent macrocyclization that enables the substitution of the disulfide bond by a tertiary lactam bridge functionalized with a variety of exocyclic moieties, including lipids, fluorophores, and charged groups. Conformational analysis in comparison with octreotide provides key information on the type of functionalization permitting the conformational mimicry of the bioactive peptide.

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Effect of O-Acetylation on the Antigenicity and Glycoconjugate Immunogenicity of the Streptococcus Pneumoniae Serotype 7F Capsular Polysaccharide

Effect of O-Acetylation on the Antigenicity and Glycoconjugate Immunogenicity of the Streptococcus Pneumoniae Serotype 7F Capsular Polysaccharide

by | Jul 4, 2025 | Immunology, Publications

Streptococcus pneumoniae is a bacterial pathogen causing diseases as severe as pneumonia, sepsis and meningitis. Most commercial pneumococcal conjugate vaccines contain the 7F serotype, which is epidemiologically relevant and highly invasive. This serotype contains an O-acetyl group at the internal L-rhamnose of its polysaccharide repeating unit. Herein we report on the role of the O-acetyl moiety of 7F polysaccharide in both antigen recognition and the induction of a protective antibody response against 7F. Fully and partially de-O-acetylated 7F polysaccharides were chemically prepared and compared with the O-acetylated counterpart in their antigenicity and immunogenicity of their tetanus toxoid glycoconjugates. These comparative studies showed a slight but consistent decrease in the antigenicity for the fully de-O-acetylated polysaccharide, but not for the partly de-O-acetylated variant. The glycoconjugates derived from the O-acetylated and the fully de-O-acetylated polysaccharides had similar sizes and polysaccharide-to-protein ratio, and all proved both to be immunogenic and induce opsonophagocytic responses in mice. Nevertheless, the immune response elicited by the O-acetylated glycoconjugate was better in both quantity and quality, proving that the O-acetyl group is not strictly necessary but also not irrelevant for the antigenicity and immunogenicity of the 7F serotype polysaccharide and its glycoconjugates.

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