In this communication, we disclose a generalizable strategy for developing agents with regulable protein-binding ability. In particular, a responsive DNA-small molecule chimera (DC) 1 consisting of two synthetic protein-binding arms and a core oligonucleotide (ODN) domain is discussed. DC 1 can be cycled from a bidentate intramolecular quadruplex form to a monodentate duplex structure, via addition of external ODN stimuli. Importantly, these distinct secondary structures of 1 lead to significantly different protein-binding abilities, with the bidentate conformation showing a 20-fold enhancement (with a 0.8 microM dissociation constant, Kd) in trypsin-binding potency.
Supramolecular chemists continuously take inspiration from complex biological systems to develop functional molecules involved in molecular recognition and self-assembly. In this regard, “smart” synthetic molecules that emulate allosteric proteins are both exciting and challenging, since many allosteric proteins can be considered as molecular switches that bind to other protein targets in a non-covalent fashion, and importantly, are capable of having their output activity controlled by prior binding to input molecules. This review discusses the foundations and passage toward the development of non-covalently operated oligonucleotide-based systems with protein-binding capacity that can be precisely regulated in an input-controlled manner.
Photonic DNA nanostructures are typically prepared by the assembly of multiple sequences of long DNA strands that are conjugated covalently to various dye molecules. Herein we introduce a non-covalent method for the construction of porphyrin-containing DNA nanowires and their networks that uses the programmed assembly of a single, very short, oligodeoxyribonucleotide sequence. Specifically, our strategy exploits a number of supramolecular binding modalities (including DNA base-pairing, metal-ion coordination, and β-cyclodextrin-adamantane derived host-guest interactions) for simultaneous nanowire assembly and porphyrin incorporation. Furthermore, we also show that the resultant DNA-porphyrin assembly can be further functionalized with a complementary “off-the-shelf” DNA binding dye resulting in photonic structures with broadband absorption and energy transfer capabilities.
In order to tackle the issue of systemic toxicity in chemotherapy, there is a need to develop novel mechanisms for the activation of protein inhibitors using biomarkers over-expressed in cancer cells. Many current strategies focus on using cancer associated enzymes as a triggering agent for prodrugs. Herein, we detail an alternative approach that harnesses a microRNA (miR-21) that is overexpressed in cancers as the trigger that activates an inhibitor of human carbonic anhydrase-II (hCA-II). Specifically, we have developed a DNA-small molecule chimera (DC) composed of an hCA-II binding lithocholic acid amide (LAA) head-group that can transition from a rigid duplex state (that does not bind appreciably to hCA) to a single stranded conformation via a miR-21 trigger. The activated single-stranded DC can project the LAA head-group into the hCA-II active site and is a robust hCA-II inhibitor (Ki of 3.12 μM). This work may spur research into developing new classes of cancer selective protein inhibitors.
Background: Oral candidiasis is by far the most common oral fungal infec!on in humans. It is caused by the fungal or--ganism Candida albicans. When the host is debilitated by other diseases and condi!ons, C. albicans, which is usually a part of the normal oral flora, can turn pathogenic and invade the host 2ssue to cause the infec2on. The purpose of this paper is to inves-gate the role of systemic diseases and medica-ons in the development of oral candidiasis. Methods: A total of 12 cases with code indica2ng oral candidiasis were collected from the University of Pi.sburgh School of Dental Medicine Dental Registry and DNA Repository. The systemic diseases and medica*ons were descrip--!vely analyzed. Results: 50% of the subjects had more than two systemic diseases. The most prevalent diseases were mental illnesses (50%), cardiovascular diseases (41.7%), and respiratory system diseases (33.3%). 50% of subjects were on polypharmacy therapies and 75% of subjects were taking medica-ons that may contribute to oral candidiasis. Among the medica!ons, an!depressants and inhala#onal cor#costeroids may have strong poten#als to cause oral candidiasis. Conclusion: Oral candidiasis is associated with having systemic diseases and intake of medica.on, espe--cially with those medica!ons can cause xerostomia. As the number of systemic diseases and medica!ons increases, the risk of developing oral candidiasis may increase too.
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