People report enjoying momentary extraverted behavior, and this does not seem to depend on trait levels of introversion-extraversion. Assuming that introverts desire enjoyment, this finding raises the question, why do introverts not act extraverted more often? This research explored a novel explanation, that trait introverts make an affective forecasting error, underpredicting the hedonic benefits of extraverted behavior. Study 1 (n = 97) found that trait introverts forecast less activated positive and pleasant affect and more negative and self-conscious affect (compared to extraverts) when asked to imagine acting extraverted, but not introverted, across a variety of hypothetical situations. Studies 2-5 (combined n = 495) found similar results using a between-subjects approach and laboratory situations. We replicated findings that people enjoy acting extraverted and that this does not depend on disposition. Accordingly, the personality differences in affective forecasts represent errors. In these studies, introverts tended to be less accurate, particularly by overestimating the negative affect and self-consciousness associated with their extraverted behavior. This may explain why introverts do not act extraverted more often (i.e., they overestimate hedonic costs that do not actually materialize) and have implications for understanding, and potentially trying to change, introverts' characteristically lower levels of happiness.
On-bead high throughput screening of a medium sized (1000–2000 Da) branched peptide boronic acid (BPBA) library consisting of 46,656 unique sequences against HIV-1 RRE RNA generated peptides with binding affinities in the low micromolar range. In particular, BPBA1 had a Kd of 1.4 µM with RRE IIB, preference for RNA over DNA (27 fold), and selectivity of up to >75 fold against a panel of RRE IIB variants. Structure-activity studies suggest that the boronic acid moiety and “branching” in peptides are key structural features for efficient binding and selectivity for the folded RNA target. BPBA1 was efficiently taken up by HeLa and A2780 cells. RNA-footprinting studies revealed that the BPBA1 binding site encompasses a large surface area that spans both the upper stem as well as the internal loop regions of RRE IIB.
We report branched peptide boronic acids (BPBAs) that bind to RRE IIB from an on-bead high-throughput screening of a 3.3.4-library (46,656 compounds). We demonstrate that boronic acids are tunable moieties that afford a novel binding mode towards RNA.
We synthesized and screened a unique 46,656-member library composed of unnatural amino acids that revealed several hits against RRE IIB RNA. Among the hit peptides identified, peptide 4A5 was found to be selective against competitor RNAs and inhibited HIV-1 Rev-RRE RNA interaction in cell culture in a p24 ELISA assay. Biophysical characterization in a ribonuclease protection assay suggested that 4A5 bound to the stem-loop region in RRE IIB while SHAPE MaP probing with 234 nt RRE RNA indicated additional interaction with secondary Rev binding sites. Taken together, our investigation suggests that HIV replication is inhibited by 4A5 blocking binding of Rev and subsequent multimerization.
The emergence of microbial resistance presents a challenge in the development of next generation therapeutics. Herein, we report the discovery of branched peptides decorated with acridine and boronic acid moieties with potent antimicrobial activity. The results revealed minimal inhibitory concentrations (MICs) as low as 1 μg/mL against ,, and . These peptides were nonhemolytic, and significantly inhibited growth of in suspension and biofilm formation. Structure-activity relationship studies suggest the acridine functional group as a driving force for the potent inhibition observed against bacteria.
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