9 research outputs found
Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages
Ala-Ala-Pro-Val (AAPV) is a bioactive tetrapeptide that inhibits human neutrophil elastase (HNE), an enzyme involved in skin chronic inflammatory diseases like psoriasis. Caged derivatives of this peptide were prepared by proper N- and C-terminal derivatisation through a carbamate or ester linkage, respectively, with two photoactive moieties, namely 7-methoxycoumarin-2-ylmethyl and pyren-2-ylmethyl groups. These groups were chosen to assess the influence of the photosensitive group and the type of linkage in the controlled photorelease of the active molecule. The caged peptides were irradiated at selected wavelengths of irradiation (254, 300, and 350 nm), and the photolytic process was monitored by HPLC-UV. The results established the applicability of the tested photoactive groups for the release of AAPV, especially for the derivative bearing the carbamate-linked pyrenylmethyl group, which displayed the shortest irradiation times for the release at the various wavelengths of irradiation (ca. 4 min at 254 nm, 8 min at 300 nm and 46 min at 350 nm).Thanks are due to the Fundação para a Ciência e Tecnologia (FCT, Portugal) for
financial support to the portuguese NMR network (PTNMR, Bruker Avance III 400-
Univ. Minho), FCT and FEDER (European Fund for Regional Development)-
COMPETE-QREN-EU for financial support through the Chemistry Research Centre of
the University of Minho (Ref. UID/QUI/00686/2013 and UID/QUI/0686/2016). A PhD
grant to A.M.S. (SFRH/BD/80813/2011) is also acknowledged.info:eu-repo/semantics/publishedVersio
Efeitos hemorreolĂłgicos e cardiovasculares da eritropoietina num modelo de rato em exercĂcio fĂsico sob a acção de drogas
Recombinant human erythropoietin
(rhEPO) has been therapeutically
used for correction of anaemia. However,
due to the increase in circulating
red blood cells (RBCs) it promotes,
thus increasing oxygen delivery to
muscles and improving performance
in sport, it has been also illegally used
as sports doping. Besides the well
known increase of hematocrit and
blood viscosity; which might cause
serious complications for the athletes,
other disturbances could occur, whose
mechanisms remain to be fully elucidated.
This study aimed to evaluate
the hemorheological and cardiovascular
effects of administration of
rhEPO to rats under chronic aerobic
exercise. A ten week-protocol was
performed in four male Wistar rat
groups: control — sedentary; rhEPO
— 50 IV/kg, 3 times/wk; exercised
(EX) — swimming for 1 hr, 3 times/
wk; EX+rhEPO. rhEPO in trained
rats promoted erythrocyte count increase,
hypertension, heart hypertro-phy, sympathetic and serotonergic
overactivation, as well as a trend to
increased oxidative stress. In conclusion,
rhEPO doping in rats under
chronic exercise promotes not only
the expected increased hematocrit,
but also other serious deleterious cardiovascular
and thromboembolic
modifications, including live risk,
which might be known and assumed
by all sports authorities, including
athletes and their physicians.info:eu-repo/semantics/publishedVersio
Photolabile protection for amino acids: studies on the release from novel benzoquinolone cages
The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time, by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson’s reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 minute).Fundação para a Ciência e Tecnologia (FCT
A photoactivable amino acid based on a novel functional coumarin-6-yl-alanine
A novel fluorescent amino acid, L-4 chloromethylcoumarin-6-yl-alanine, was obtained from tyrosine by a Pechmann reaction. The assembly of the heterocyclic ring at the tyrosine side chain could be achieved before or after incorporation of tyrosine into a dipeptide, and amino acid and dipeptide ester conjugates were obtained by coupling to a model N-protected alanine. The behaviour of one of the fluorescent conjugates towards irradiation was studied in a photochemical reactor at different wavelengths (254, 300, 350 and 419 nm). The photoreaction course in methanol/HEPES buffer solution (80:20) was followed by HPLC/UV monitoring. It was found that the novel unnatural amino acid could act as a fluorescent label, due to its fluorescence properties, and, more importantly, as a photoactivable unit, due to the short irradiation times necessary to cleave the ester bond between the model amino acid and the coumarin-6-yl-alanine.Universidade do Minho (UM)Fundação para a Ciência e a Tecnologia (FCT