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La química al servicio de bibliotecas codificadas por ADN

Resumen

Tipo:
Oferta Tecnológica
Referencia:
TODE20170802002
Publicado:
15/08/2017
Caducidad:
15/08/2018
Resumen:
Una universidad alemana ha mejorado con éxito la resistencia de bibliotecas codificadas por ADN. En comparación con los procedimientos actuales, esta tecnología mejora la estabilidad del cribado de alto rendimiento cuando se utilizan organocatalizadores acídicos u otros productos químicos más agresivos, y tiene unos costes más reducidos que el cribado de alto rendimiento convencional. La universidad busca compañías farmacéuticas con acceso al espacio químico biológicamente relevante, inaccesible con las bibliotecas convencionales. El objetivo es establecer acuerdos de licencia y cooperación en materia de investigación.

Details

Tittle:
Enabling chemistry for DNA-encoded screening libraries
Summary:
A German university successfully improved the resistance of DNA-encoded screening libraries. Pharmaceutical companies will have access to biologically relevant chemical scope that is inaccessible with conventional DNA-encoded libraries. The university is offering a license agreement and a research cooperation agreement.
Description:
The need of new drugs is high in many medical indications, for instance in oncology, and infectious diseases. However, the success rate of drug research and development has declined to unsustainable levels. As conventional high throughput screening of large compound libraries often fails to deliver compounds, the de novo identification of bioactive small molecules represents a significant hurdle in drug research. DNA-encoded small molecule libraries (DELs) have emerged as a cost-efficient, validated screening method of very large chemical space. These libraries consist of DNA-tagged small molecules. They can be pooled and screened on drug targets by affinity-based selection. Bioactive compounds are efficiently identified by DNA sequencing. Current library synthesis strategies, though, can make use of only a very limited set of chemical reactions, thus delivering large numbers but low diversity. Notably, access to encoded libraries of drug-like heterocycles is currently lacking.

The invention of a German university addresses this severe limitation. It exploits the stability of oligopyrimidine adapter sequences to a large variety of reaction conditions, and reagents such as transition metal catalysts and acidic organocatalysts. Thus, the invention enables efficient access to diverse heterocyclic structures conjugated to oligopyrimidine sequences from simple and readily available starting materials by a large variety of catalysts. These oligonucleotide-heterocycle conjugates are readily ligated to coding DNA sequences. Combinatorial mix-and-split synthesis yielded a proof-of-concept screening library counting 15,000 molecules. The library is based on biologically relevant heterocyclic core structures that are found in natural products, drug candidates and approved drugs. It is currently expanded to diverse classes of drug-like structures comprising heterocycles and macrocycles.

The university is offering a license agreement and a research cooperation agreement. This profile addresses the pharmaceutical industry in need for enhanced drug screening.The university is also open for a research cooperation in order to enhance the application.
Advantages and Innovations:
In comparison to current procedures this invention is improving the stability of high throughput screenings when it comes to the use of acidic organocatalysts or other more aggressive chemicals. The invention thus enhances the currently limited set of chemical reactions used in screenings. Other advantages are:

- Handling of large encoded compound screening libraries
- Access to biologically relevant chemical space that is inaccessible by conventional DNA-encoded libraries: encoded natural product- and drug-derived compound classes
- Efficient and rapid screening on target proteins by selection
- Extremely reduced costs in comparison to conventional high-throughput screening
- Accelerated identification of starting points for drug development programs
Stage of Development:
Under development/lab tested
IPs:
Patent(s) applied for but not yet granted
CommeR Statunts Regarding IPR Status:
A US-American patent application has been filed.

Partner sought

Type and Role of Partner Sought:
The invention is offered to pharmaceutical producers and developers, biotech companies and non-profit organisations for drug identification and development programs. Pharmaceutical producers with its own product development can use the screening library in-house. Chemical companies could offer the library as a service to identify potential candidates for new drugs.
The university is offering a license and research cooperation agreement.The university is also open for a research cooperation in order to enhance the application.

Client

Type and Size of Client:
University
Already Engaged in Trans-National Cooperation:
Si
Languages Spoken:
English
German

Keywords

Technology Keywords:
06002001 Bioquímica / biofísica
03004007 Pharmaceutics
06001015 Productos farmacéuticos / medicamentos
05001001 Química analítica