Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.

The combinatorial synthesis of bicyclic privileged structures or privileged substructures

The present invention relates to compounds, methods and pharmaceutical compositions for inhibiting proteases, particularly serine proteases, and more particularly HCV NS3 proteases. The compounds, and the compositions and methods that utilize them, can be used, either alone or in combination to inhibit viruses, particularly HCV virus.

Inhibitors of serine proteases, particularly hepatitis C virus NS3 protease

Isolated, antigenic polypeptides including a prehairpin intermediate conformation of gp41 and vectors encoding such polypeptides are provided. Antibodies that bind to a prehairpin intermediate conformation of gp41 and methods of making antibodies a that bind to prehairpin intermediate conformation of gp41 are also provided. Vaccines against a prehairpin intermediate conformation of gp41, as well as methods of treating subjects infected with HIV, preventing HIV infection, and inhibiting HIV-mediated activities are also provided. Methods of screening compounds that bind to an isolated, prehairpin intermediate conformation of gp41 are further provided.

https://www.pnas.org/content/pnas/105/10/3739.full.pdf

A fusion-intermediate state of hiv-1 gp41 targeted by broadly neutralizing antibodies

http://csmres.co.uk/cs.public.upd/article-downloads/Axel%20Vater,%20%20and%20Sven%20Klussmann%20Drug%20Discovery%20Today%20Volume%2020,%20Issue%201,%20January%202015,%20Pages%20147–155_a42064.pdf

Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics.

The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

Inhibitors of serine proteases, particularly hcv ns3-ns4a protease

Methods for engineering a nucleic acid sensor molecule are provided. Biosensors comprise a plurality of nucleic acid sensor molecules labeled with a first signaling moiety and a second signaling moiety. The nucleic acid sensor molecules recognizes target molecules which do not naturally bind to DNA. Binding of a target molecule to the sensor molecules triggers a change in the proximity of the signaling moieties which leads to a change in the optical properties of the nucleic acid sensor molecules on the biosensor. Reagents and systems for performing the method are also provided. The method is useful in diagnostic applications and drug optimization.

Nucleic acid sensor molecules and methods of using same

Methods for engineering a target activated biosensor are provided Biosensors comprise a plurality of nucleic acid sensor molecules labeled with a first signaling moiety and a second signaling moiety The nucleic acid sensor molecules recognizes target molecules which do not naturally bind to DNA Binding of a target molecule to the sensor molecules triggers a change in the proximity of the signaling moieties which leads to a change in the optical properties of the nucleic acid sensor molecules on the biosensor Reagents and systems for performing the method are also provided The method is useful in diagnostic applications and drug optimization

Target activated nucleic acid biosensor and methods of using same

The invention provides nucleic acid therapeutics and methods for using these nucleic acid therapeutics in the treatment of complement-related disorders.

Aptamer therapeutics useful in the treatment of complement-related disorders

Methods of treating complement-mediated ocular disorders by administering agents that inhibit a subject's complement component in an amount sufficient to treat the ocular disorder wherein, in a selected embodiment, said agent is an anti-complement aptamer that, in a preferred embodiment, is an anti-C5 aptamer.

Complement binding aptamers and anti-c5 agents useful in the treatment of ocular disorders

Materials and methods are provided for producing aptamer therapeutics having improved pharmacokinetic and pharmacodymanic properties, as well as increased target valency. The aptamers produced by the methods of the invention are useful as therapeutics for treating disease.

Multivalent aptamer therapeutics with improved pharmacodynamic properties and methods of making and using the same

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