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Projeto de investigação
A MINIMAL PROTEIN PHOSPHATASE PTEN - A CANCER THERAPEUTIC AGENT
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Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity
Publication . Pina, Ana S.; Morgado, Leonor; Duncan, Krystyna L.; Carvalho, Sara; Carvalho, Henrique F.; Barbosa, Arménio J. M.; de P. Mariz, Beatriz; Moreira, Inês P.; Kalafatovic, Daniela; Morais Faustino, Bruno M.; Narang, Vishal; Wang, Tong; Pappas, Charalampos G.; Ferreira, Isabel; Roque, Ana Cecília Afonso; Ulijn, Rein V.; UCIBIO - Applied Molecular Biosciences Unit; DQ - Departamento de Química; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; ROYAL SOC CHEMISTRY
We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH2(P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state withKD= 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY through the KVYF terminus and this binding event disrupts the assembled structure. In absence of the target micellar aggregate, P7 was further found to dynamically alternate between multiple conformations, with a preferred hairpin-like conformation that was shown to contribute to supramolecular ligand binding. Three identified phages presented appreciable binding, and two showed to catalyze the hydrolysis of a modelpara-nitro phenol phosphate substrate, with P7 demonstrating conformation-dependent activity with a modestkcat/KM= 4 ± 0.3 × 10−4M−1s−1
Tunable Gas Sensing Gels by Cooperative Assembly
Publication . Hussain, Abid; Semeano, Ana T. S.; Palma, Susana I. C. J.; Pina, Ana S.; Almeida, José; Medrado, Bárbara F.; Pádua, Ana C. C. S.; Carvalho, Ana L.; Dionísio, Madalena; Li, Rosamaria W. C.; Gamboa, Hugo; Ulijn, Rein V.; Gruber, Jonas; Roque, Ana C. A.; DQ - Departamento de Química; UCIBIO - Applied Molecular Biosciences Unit; LAQV@REQUIMTE; DF – Departamento de Física; LIBPhys-UNL; WILEY-V C H VERLAG GMBH
The cooperative assembly of biopolymers and small molecules can yield functional materials with precisely tunable properties. Here, the fabrication, characterization, and use of multicomponent hybrid gels as selective gas sensors are reported. The gels are composed of liquid crystal droplets self-assembled in the presence of ionic liquids, which further coassemble with biopolymers to form stable matrices. Each individual component can be varied and acts cooperatively to tune gels' structure and function. The unique molecular environment in hybrid gels is explored for supramolecular recognition of volatile compounds. Gels with distinct compositions are used as optical and electrical gas sensors, yielding a combinatorial response conceptually mimicking olfactory biological systems, and tested to distinguish volatile organic compounds and to quantify ethanol in automotive fuel. The gel response is rapid, reversible, and reproducible. These robust, versatile, modular, pliant electro-optical soft materials possess new possibilities in sensing triggered by chemical and physical stimuli.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
OE
Número da atribuição
SFRH/BPD/97585/2013