Dr. William Goldring

Research

The Goldring research group is engaged in a synthetic study of natural products and biological molecules which possess interesting structures and important biological activity for the treatment of human diseases, such as cancer, tuberculosis, and malaria. Using synthesis, we aim to construct these molecules in the laboratory to develop a better understanding of their structures and ability to regulate biological function. Therefore, synthesis, and the development of its methods, play a central role in our research programs.

 

Target Based Synthesis

Our target based natural product synthesis program aims to construct natural molecules of biological interest. Together with the challenge of synthesis, we aim to understand the structure of these molecules and the role they play in regulating biological processes. We are currently pursuing a number of challenging targets, such as the anti-malarial agent anthecularin, the anti-bacterial agent coleophomone A, and umbelactone. A key aspect of our synthetic program is the development of new methodologies, and the exploration of new routes to structures ranging from the unique to those which are well known.

 

The natural and related molecules synthesised in our laboratory are evaluated, as part of a collaboration, for their biological activity. Therefore, the outcome of our synthetic research has an impact on the development of medicines for use in the treatment of important human health issues such as; cancer, heart disease, and infection.

 

Building Blocks for use in Synthesis

The construction of synthetic building blocks, and the development of new methods and routes to these valuable structures, has a significant impact on our research activities. For example, using an appropriately designed structure we are able to study and exploit chemical processes employed by Nature. When based on speculation regarding the biosynthesis of a natural product, these structures could help to unravel their biogenetic origin. Other building blocks inspired by natural products are used as key intermediates in synthesis for the construction of complex molecules. For example, our group recently constructed butenolide structures, based on natural umbelactone, for future applications in natural product synthesis, such as anthecularin.

 

Many of our current target molecules possess complex and synthetically challenging structures, whose assembly in Nature is completely unknown. Therefore, using synthesis to construct important synthetic building blocks, we aim to unravel the mystery of structures which possess an unprecedented molecular architecture and biological function.

 

Drug Development and Delivery

Our approach to the development and delivery of therapeutic treatments for human disease involves studies in separate areas, such as small molecule synthesis and gene therapy.

The world-wide re-emergence of tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis which affects the lungs and other vital organs, has prompted efforts towards its prevention and treatment. Since the World Health Organization declared TB a global emergency in 1993 the number of resistant TB cases in Northern Ireland has steadily increased from 2% to 10%. In recognition of this global problem our laboratory recently constructed a small library of natural and related matricaria esters, characterised by a core diene-diyne structure. The natural members of this family of molecules possess anti-mycobacterial activity, and therefore represent a potential treatment for TB. Therefore, using a natural product structure as a template, we aim to synthesise a library of analogue molecules for biological evaluation, which complements other related activities within the School.

 

As part of a collaborative research program in gene therapy, our group is developing reliable, targeted vectors to deliver genetic material into cells for the treatment of diseases, such as cancer. This project, which receives support from the British Council, is conducted in collaboration with Weill Cornell Medical College – Qatar. Our design for the construction of non-viral delivery vehicles includes; (i) a targeting ligand for the selective recognition of diseases cells, eg. folate for cancer cells, (ii) a non-polar core to protect the genetic cargo from degradation enzymes and to facilitate its delivery into the cell, and (iii) a cationic head group for binding of the genetic cargo. Biophysical characterisation studies of the vector-genetic material complex, together with assays which evaluate the toxicity of the synthesised vehicle and its ability to bind and protect the genetic material are performed by colleagues at WCMC-Q.