Anionic glycolipids related to glucuronosyldiacylglycerol inhibit protein kinase Akt

Vetro, M.; Costa, Barbara; Donvito, Giulia; Arrighetti, Noemi; Cipolla, Laura; Perego, Paola; Compostella, Federica; Ronchetti, Fiamma; Colombo, Diego

doi:10.1039/c4ob01602e

Cited by 15 publications

(17 citation statements)

References 37 publications

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“…Glycoglycerolipids occur widely in marine algae [ 5 , 6 , 7 , 8 ], cyanobacteria [ 9 , 10 , 11 ] and higher plants. The natural glycoglycerolipids possess various biological activities, such as anti-tumor [ 12 , 13 ], anti-viral [ 14 , 15 , 16 , 17 ], and anti-inflammatory activities [ 18 ], which make them valuable molecular targets for further investigation [ 19 ]. In our previous work [ 20 , 21 , 22 ] synthetic aminoglycoglycerolipids derived from marine natural product 1,2-dipalmitoyl-3-( N -palmitoyl-6′-amino-6′-deoxy-α- d -glucosyl)- sn -glycerol (AGGL, Figure 1 ) [ 23 ] were found to possess notable anti-IAV activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anti-Influenza A Virus Activity of 6′-amino-6′-deoxy-glucoglycerolipids Analogs

Ren

Zhang

et al. 2016

Marine Drugs

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A series of aminoglucoglycerolipids derivatives had been synthesized, including 6′-acylamido-glucoglycerolipids 1a–1f and corresponding 2′-acylamido-glucoglycerolipids 2a–2c bearing different fatty acids, glucosyl diglycerides 3a–3e bearing different functional groups at C-6′ and ether-linked glucoglycerolipids 4a–4c with double-tailed alkyl alcohol. The anti-influenza A virus (IAV) activity was evaluated by the cytopathic effects (CPE) inhibition assay. The results indicated that the integral structure of the aminoglycoglycerolipid was essential for the inhibition of IAV in MDCK cells. Furthermore, oral administration of compound 1d was able to significantly improve survival and decrease pulmonary viral titers in IAV-infected mice, which suggested that compound 1d merited further investigation as a novel anti-IAV candidate in the future.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Anti-Influenza A Virus Activity of 6′-amino-6′-deoxy-glucoglycerolipids Analogs

Ren

Zhang

et al. 2016

Marine Drugs

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“…The use of peptide-based materials for diagnostic purposes holds a great deal of potential for further development and applications. It is tempting to suggest that methods for the de novo prediction of interacting sequences can be used not only to mimic antigen–antibody interactions but complex (even multivalent) interactions in general [58,59,60,61,62]. The latter are an extremely challenging class of targets, due to the peculiar conformational and chemical characteristics of the interacting surfaces; the selection, design, and optimal display of mimics of the regions that underpin protein–protein molecular recognition can be aptly used to detect specific PPIs in normal vs. transformed cells.…”

Section: Discussionmentioning

confidence: 99%

Peptides for Infectious Diseases: From Probe Design to Diagnostic Microarrays

et al. 2019

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Peptides and peptidomimetics have attracted revived interest regarding their applications in chemical biology over the last few years. Their chemical versatility, synthetic accessibility and the ease of storage and management compared to full proteins have made peptides particularly interesting in diagnostic applications, where they proved to efficiently recapitulate the molecular recognition properties of larger protein antigens, and were proven to be able to capture antibodies circulating in the plasma and serum of patients previously exposed to bacterial or viral infections. Here, we describe the development, integration and application of strategies for computational prediction and design, advanced chemical synthesis, and diagnostic deployment in multiplexed assays of peptide-based materials which are able to bind antibodies of diagnostic as well as therapeutic interest. By presenting successful applications of such an integrated strategy, we argue that they will have an ever-increasing role in both basic and clinical realms of research, where important advances can be expected in the next few years.

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“…We suggest that these methods of drug and peptide design could be conceivably coupled to the design of polyvalent systems that allow the simultaneous binding of multiple ligands to a certain target, mimicking the types of interactions that are widespread in biology [ 63 ]. The availability of chemical synthesis methods for the access to complex mimics of natural products or chemical-biology probes [ 64 , 65 , 66 , 67 , 68 ], and the explosion of chemical methods for the display of multiple ligands (through nanoparticles, bio-inspired polymers etc...) can indeed help the development of multivalent systems that we see as potentially suitable for vaccination and patient diagnostics: in these cases, the simultaneous presentation of multiple determinants of Ab-recognition from the antigens of a certain pathogen may help trigger protective response against it [ 69 , 70 , 71 , 72 ]. In the case of small molecule drugs, multi-presentation approaches may become particularly useful when targeting large multi-component complexes.…”

Section: Discussionmentioning

confidence: 99%

Targeting Difficult Protein-Protein Interactions with Plain and General Computational Approaches

Ferraro

Colombo

2018

Molecules

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Investigating protein-protein interactions (PPIs) holds great potential for therapeutic applications, since they mediate intricate cell signaling networks in physiological and disease states. However, their complex and multifaceted nature poses a major challenge for biochemistry and medicinal chemistry, thereby limiting the druggability of biological partners participating in PPIs. Molecular Dynamics (MD) provides a solid framework to study the reciprocal shaping of proteins’ interacting surfaces. Here, we review successful applications of MD-based methods developed in our group to predict interfacial areas involved in PPIs of pharmaceutical interest. We report two interesting examples of how structural, dynamic and energetic information can be combined into efficient strategies which, complemented by experiments, can lead to the design of new small molecules with promising activities against cancer and infections. Our advances in targeting key PPIs in angiogenic pathways and antigen-antibody recognition events will be discussed for their role in drug discovery and chemical biology.

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Anionic glycolipids related to glucuronosyldiacylglycerol inhibit protein kinase Akt

Abstract: Long chain GlcADG analogues synthesized as PI3P mimics inhibited isolated Akt and proliferation of human ovarian carcinoma IGROV-1 cells.

Cited by 15 publications

References 37 publications

Synthesis and Anti-Influenza A Virus Activity of 6′-amino-6′-deoxy-glucoglycerolipids Analogs

Synthesis and Anti-Influenza A Virus Activity of 6′-amino-6′-deoxy-glucoglycerolipids Analogs

Peptides for Infectious Diseases: From Probe Design to Diagnostic Microarrays

Targeting Difficult Protein-Protein Interactions with Plain and General Computational Approaches

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