We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >8...

Abstract Antibiotic resistance threatens clinical control of bacterial infections while the genetic adaptability microbes continues to outpace small-molecule development. The combinatorial diversity antibodies offers a solution this problem. However, under normal circumstances polymeric glycans surfaces avoid adaptive recognition by not binding MHC molecules. Thus, they are T cell independent a...

Recent evidence suggests that many complex diseases are caused by genetic variations that play regulatory roles in controlling gene expression. Most genetic studies focus on nonsynonymous variations that can alter the amino acid composition of a protein and are therefore believed to have the highest impact on phenotype. Synonymous variations, however, can also play important roles in disease pa...

The affinity of various mutant lac DNAs for the lac repressor was examined by means of a competition binding assay. The results indicate that there exist at least two binding sites for the lac repressor. The primary binding site is coincidental with the operator, as defined by genetic studies. Mutations of the promoter or the Z gene have little or no effect on the repressor binding properties o...

Pakistan is a part of South Asia that modern humans encountered soon after they left Africa ~50 - 70,000 years ago. Approximately 9,000 years ago they began establishing cities that eventually expanded to represent the Harappan culture, rivalling the early city states of Mesopotamia. The modern state constitutes the north western land mass of the Indian sub-continent and is now the abode of alm...

the affinity of low density lipoprotein(ldl) to its receptor is very important, because most of ldl-uptake pathway is done by the ldl receptor and the change in size of ldl particle and the modification in its components may affect the ldl affinity for its receptor. in this study, the effects of a powerful lipid-soluble antioxidant “ubiquinol-10” have been investigated on the affinity of ldl to...

Upon binding to estrogens, the ERα nuclear receptor acts as a transcription factor and mediates a multitude of cellular functions central to health and disease. Herein, using isothermal titration calorimetry (ITC) and circular dichroism (CD) in conjunction with molecular modeling (MM), we analyze the effect of symmetric introduction of single nucleotide variations within each half-site of the e...

In high-altitude vertebrates, adaptive changes in blood-O(2) affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O(2) affinity and/or responsiveness to allosteric effectors that modulate Hb-O(2) affinity. This mode of genotypic specialization is considered typical of mammalian species that are high-altitude natives. Here we investigated genetically based...

C-reactive protein (CRP) is involved in host defense, regulation of inflammation, and modulation of autoimmune disease. Although the presence of receptors for CRP on phagocytes has been inferred for years, their identity was determined only recently. FcgammaRIa, the high-affinity IgG receptor, binds CRP with low affinity, whereas FcgammaRIIa, the low-affinity IgG receptor, binds CRP with high a...