11 research outputs found
Synthesis of phosphoramidite monomers equipped with complementary bases for solid-phase DNA oligomerization
We describe the preparation of two monomers that bear complementary nucleobases at the edges (guanine-2â˛-deoxycytidine and 2- aminoadenine-2â˛-deoxyuridine) and that are conveniently protected and activated for solid-phase automated DNA synthesis. We report the optimized synthetic routes leading to the four nucleobase derivatives involved, their crosscoupling reactions into dinucleobase-containing monomers, and their oligomerization in the DNA synthesizerFunding from the European Research Council (ERC-Starting Grant 279548 PROGRAM-NANO) and MINECO (CTQ2014-57729-P, SAF2017-87305-R and CTQ2017- 84727-P) is gratefully acknowledge
Peptide-oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic
Peptide-based structures can be designed to yield artificial proteins with specific folding patterns and functions. Template-based assembly of peptide units is one design option, but the use of two orthogonal self-assembly principles, oligonucleotide triple helix and a coiled coil protein domain formation have never been realized for de novo protein design. Here, we show the applicability of peptideâoligonucleotide conjugates for self-assembly of higher-ordered protein-like structures. The resulting nano-assemblies were characterized by ultraviolet-melting, gel electrophoresis, circular dichroism (CD) spectroscopy, small-angle X-ray scattering and transmission electron microscopy. These studies revealed the formation of the desired triple helix and coiled coil domains at low concentrations, while a dimer of trimers was dominating at high concentration. CD spectroscopy showed an extraordinarily high degree of Îą-helicity for the peptide moieties in the assemblies. The results validate the use of orthogonal self-assembly principles as a paradigm for de novo protein design
Selective N-terminal acylation of peptides and proteins with a Gly-His tag sequence
His-tagged proteins can undergo N-terminal acylation as an undesired side-reaction. Here, the authors utilize this to develop a method for highly selective acylation and further modification of peptides and proteins using an optimized His sequence and 4-methoxyphenyl esters as acyl donors
Independent and combined association of overall physical fitness and subjective well-being with fibromyalgia severity : the al-Ăndalus project
PURPOSE: The present study aimed: (1) to test the associations of overall physical fitness and subjective well-being with fibromyalgia severity and (2) to determine whether the combination of overall physical fitness and subjective well-being is associated with fibromyalgia severity among adult women patients. METHODS: This cross-sectional study included 424 participants from Andalusia, southern Spain. Overall physical fitness and the components of subjective well-being (positive affect, negative affect and cognitive well-being), and fibromyalgia severity were assessed using the Functional Senior Physical Fitness Test Battery, the Positive and Negative Affect Schedule, the Satisfaction With Life Scale, and the Fibromyalgia Impact Questionnaire, respectively. RESULTS: Overall physical fitness (β = -.23), positive affect (β = -.18), negative affect (β = .26), and cognitive well-being (β = -.18) were all associated with fibromyalgia severity. The patients with the highest overall physical fitness and increased subjective well-being reported ~15 % lower fibromyalgia severity than those with the lowest fitness and poorest subjective well-being (Cohen's d > 1.0). CONCLUSION: Our results suggest that higher levels of overall physical fitness and subjective well-being are independently associated with lower fibromyalgia severity. Moreover, patients with higher overall physical fitness and increased subjective well-being (high positive affect, low negative affect, or high cognitive well-being) reported lower fibromyalgia severity than those with low levels of overall physical fitness and subjective well-being
Poly(amido amine)-Based Mannose-Glycodendrimers As Multielectron Redox Probes for Improving Lectin Sensing
An easy-to-prepare series of electroactive polyÂ(amido
amine) (PAMAM)-based
dendrimers of generations G0 to G2 having mannopyranosylferrocenyl
moieties in the periphery to detect carbohydrateâprotein interactions
is reported. The synthesis involved the functionalization of the PAMAM
surface with azidomethylferrocenyl groups and subsequent coupling
of mannoside units by the CuÂ(I)-catalyzed Huisgen reaction. The binding
affinity of the series of electroactive glycodendrimers was studied
by isothermal titration calorimetry (ITC) and differential pulse voltammetry
(DPV). Upon complexation of the glycodendrimers conjugates with prototypical
concanavalin A (Con A), voltammograms showed a decrease of the peak
current. Such dendrimers showed a notable improvement of redox sensing
abilities toward Con A when compared with mono- and divalent analogues,
based on both the glycoside multivalent and ferrocene dendritic effects
The discordance between subjectively and objectively measured physical function in women with fibromyalgia: association with catastrophizing and self-efficacy cognitions. The al-Ăndalus project
Purpose: People with fibromyalgia experience a disagreement between patient-reported (i.e., subjective) and performance-based (i.e., objective) status. This study aimed to (i) corroborate the discordance between subjectively and objectively measured physical function and (ii) examine whether catastrophizing (worrying, pain magnifying, and helpless cognitions) and self-efficacy (believing capable to manage pain) are independently associated with this discordance. Methods: This population-based cross-sectional study included 405 women with fibromyalgia and 193 age-matched female controls. Participants completed the Pain Catastrophizing Scale, Chronic Pain Self-efficacy Scale, and physical functioning subscales of the Revised Fibromyalgia Impact Questionnaire and Short Form-36 (SF-36) health survey. Objective physical function was measured with the Senior Fitness Test battery. Subjective and objective physical functions were expressed as deviation from the general population in standard deviation (SD) units using means and SD of the control group. Results: In fibromyalgia, subjective physical function was worse than objective physical function (p < 0.001). Higher catastrophizing was consistently associated with greater discordance between subjective and objective physical function, while self-efficacy was only significantly associated with this discordance when subjective physical function was assessed by means of the SF-36. Conclusions: Subjective physical function is more impaired than objective physical function in fibromyalgia, yet both are markedly impaired. Catastrophizing cognitions are associated with this discordance. In particular, high catastrophizing may promote a feeling of reduced ability to do meaningful activities of daily living (i.e., restrictions) that people with fibromyalgia are actually able to. Therefore, catastrophizing should be assessed and potentially targeted when focusing on improving physical function in fibromyalgia.Implications for rehabilitation Rehabilitation should focus on physical exercise programs to help women with fibromyalgia to improve their reduced physical function. In rehabilitation settings, physical function of people with fibromyalgia should be evaluated by both subjective and objective assessments to fully understand physical functioning and to test the existence of discordance between both assessments. In case of a large discordance between subjective and objective physical function, a physical exercise program might be better complemented with cognitive management techniques to reduce catastrophizing and subjective physical dysfunction. When people with fibromyalgia experience high levels of catastrophizing, subjective assessments seem to be poor indicators of physical function
βâCyclodextrin-Bearing Gold Glyconanoparticles for the Development of Site Specific Drug Delivery Systems
Three novel gold nanoparticles containing
multiple long, flexible
linkers decorated with lactose, β-cyclodextrin, and both simultaneously
have been prepared. The interaction of such nanoparticles with β-d-galactose-recognizing lectins peanut agglutinin (PNA) and
human galectin-3 (Gal-3) was demonstrated by UVâvis studies.
Gal-3 is well-known to be overexpressed in several human tumors and
can act as a biorecognizable target. This technique also allowed us
to estimate their loading capability toward the anticancer drug methotrexate
(MTX). Both results make these glyconanoparticles potential site-specific
delivery systems for anticancer drugs
Peptide Half-Life Extension: Divalent, Small-Molecule Albumin Interactions Direct the Systemic Properties of Glucagon-Like Peptide 1 (GLP-1) Analogues
Noncovalent binding of biopharmaceuticals
to human serum albumin
protects against enzymatic degradation and renal clearance. Herein,
we investigated the effect of mono- or divalent small-molecule albumin
binders for half-life extension of peptides. For proof-of-principle,
the clinically relevant glucagon-like peptide 1 (GLP-1) was functionalized
with diflunisal, indomethacin, or both. In vitro, all GLP-1 analogues
had subnanomolar GLP-1 receptor potency. Surface plasmon resonance
revealed that both small molecules were able to confer albumin affinity
to GLP-1 and indicated that affinity is increased for divalent analogues.
In lean mice, the divalent GLP-1 analogues were superior to monovalent
analogues with respect to control of glucose homeostasis and suppression
of food intake. Importantly, divalent GLP-1 analogues showed efficacy
comparable to liraglutide, an antidiabetic GLP-1 analogue that carries
a long-chain fatty acid. Finally, pharmacokinetic investigations of
a divalent GLP-1 analogue demonstrated a promising gain in circulatory
half-life and absorption time compared to its monovalent equivalent