Direct Comparison of Linear and Macrocyclic Compound Libraries as a Source of Protein Ligands

There has been much discussion of the potential desirability of macrocyclic molecules for the development of tool compounds and drug leads. But there is little experimental data comparing otherwise equivalent macrocyclic and linear compound libraries as a source of protein ligands. In this Letter, we probe this point in the context of peptoid libraries. Bead-displayed libraries of macrocyclic and linear peptoids containing four variable positions and 0–2 fixed residues, to vary the ring size, were screened against streptavidin and the affinity of every hit for the target was measured. The data show that macrocyclization is advantageous, but only when the ring contains 17 atoms, not 20 or 23 atoms. This technology will be useful for conducting direct comparisons between many different types of chemical libraries to determine their relative utility as a source of protein ligands

Additional file 1 of NKD2 is correlated with the occurrence, progression and prognosis of thyroid carcinoma

Additional file 1: Table S1. Clinical features of thyroid cancer patients

Additional file 2 of NKD2 is correlated with the occurrence, progression and prognosis of thyroid carcinoma

Additional file 2: Table S2. GSEA result

Additional file 3 of NKD2 is correlated with the occurrence, progression and prognosis of thyroid carcinoma

Additional file 3. The original results of western blot

Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor

Perfluoroalkyl acids (PFAAs) have been reported to interfere with the endocrine system in vivo by mimicking endogenous hormone activities and causing adverse effects. Some exoestrogens bind to estrogen receptor (ER) and subsequently induce an ER-mediated response. The transcriptional activity of ER is regulated by its distinct conformational states that are the results of ligand binding. In this work, a biosensor based on surface plasmon resonance (SPR) technique was developed which can discriminate between agonist and antagonist of human ERα (hERα) by monitoring the conformation state of the protein induced by ligand binding. The biosensor utilized the specific interaction between hERα and conformation-selective peptides. Six PFAAs with different chain lengths and acid groups were tested by the biosensor, and perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were found to be ER agonists. Kinetic analyses of direct interaction between PFAAs and hERα by SPR revealed that PFOS and PFOA were both weak binders of ER with <i>K</i>_D values of 2.19 and 107 μM respectively, whereas the other four PFAAs did not bind with ER. To understand the differences in ER binding affinity and estrogenic activity among the six PFAAs, molecular docking based on the crystal structure of hERα ligand binding domain was performed. PFOS and PFOA were efficiently docked with hERα and formed hydrogen bonds with Arg394 in a manner similar to estradiol. Overall, the two 8-carbon PFAAs were assessed as weak agonists of hERα and are of potential concern

Chlorantraniliprole as a candidate pesticide used in combination with the attracticides for lepidopteran moths - Fig 1

<p>The toxicities of <i>Helicoverpa armigera</i> moths after treated by 23 different insecticides following 24 h exposure at the concentration of 100–500 mg a.i. L^-1 (A) and 1 mg a.i. L^-1 (B).</p

Lethal time (LT₅₀) of three insecticides to the moths of three lepidopteran pests.

<p>Lethal time (LT₅₀) of three insecticides to the moths of three lepidopteran pests.</p

The toxicities of <i>Spodoptera litura</i> moths after treated by 5 different insecticides following 24 h exposure at the concentration of 100 and 1 mg a.i. L^-1.

<p>The toxicities of <i>Spodoptera litura</i> moths after treated by 5 different insecticides following 24 h exposure at the concentration of 100 and 1 mg a.i. L^-1.</p

The toxicities of <i>Agrotis ipsilon</i> moths after treated by 5 different insecticides following 24 h exposure at the concentration of 100 and 1 mg a.i. L^-1.

<p>The toxicities of <i>Agrotis ipsilon</i> moths after treated by 5 different insecticides following 24 h exposure at the concentration of 100 and 1 mg a.i. L^-1.</p

Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of <i>Monopterus albus</i>

<div><p>Background</p><p>The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (<i>Monopterus albus</i>). How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male) from the rice field eel to investigate changes in transcriptional level during the sex reversal process.</p><p>Results</p><p>Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes). These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes’ expression patterns were validated by RT-qPCR. The expression of <i>spef2</i>, <i>maats1</i>, <i>spag6</i> and <i>dmc1</i> were abundant in testis, but was barely detected in females, while the <i>17β-hsd12</i>, <i>zpsbp3</i>, <i>gal3</i> and <i>foxn5</i> were only expressed in ovary.</p><p>Conclusion</p><p>This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.</p></div