New-generation drugs
The Center for Multifunctional Biomolecular Drug Design (CEMBID) aims to develop and investigate novel modular designs for assembly of well-defined multifunctional biomolecular drugs. Multifunctional drugs are composed of two or more functional units and are challenging and expensive to prepare. Moreover, because traditional medicines are most often based on small molecules that act on the whole body, healthy cells are exposed to the drug often resulting in severe side-effects. Targeted therapies known today are often neglected for economic reasons. Therefore, CEMBID will develop a novel platform for developing multifunctional drugs using a technology that can be provide better and cheaper targeted treatments for patients.
We aim to synthesize multifunctional drugs that can target and deliver bioactive drugs to specific sites as well as drugs that are capable of non-invasive imaging of disease condition and progression. Through the combination of different functionalities such as disease-targeting ligands with drug and imaging payloads, it is possible to achieve high selectivity and efficiency of the drug.
Strategies
Using oligonucleotide linkers as “handles”, researchers working at CEMBID will assemble individual molecules into well-defined multifunctional drugs. A recently developed approach known as DNA-Templated Protein Conjugation, which is site-selective and has high reaction rates, will be employed. The approach is both versatile, efficient, and scalable and will be used for screening and development of the multifunctional drugs that will be validated and exemplified in two major human diseases, cancer and atherosclerotic plaques.
To optimize the effect of the developed drugs, we will employ strategies for pharmacokinetic modification to minimize rapid renal clearance. If a drug is rapidly cleared in the kidneys, sufficient drug accumulation at the disease site is not allowed. Furthermore, we aim to combine bioimaging and therapeutic properties through the inclusion of imaging moieties within the multifunctional drugs. In some diseases, it is desirable to have a controlled release of the drug after cellular entry. Integrated cleavable linkers, such as disulphides that are reduced in the cytoplasmic environment, will be placed between the oligonucleotide and the small molecule drug.
