Download Combinatorial Platinum(IV)-Peptide/Co-drug Conjugates as Multimodal Targeted Anticancer Agents.

NUS Graduate School for Integrative Sciences and Engineering
Research Project Write-up
Title of Project :
Combinatorial Platinum(IV)-Peptide/Co-drug Conjugates
as Multimodal Targeted Anticancer Agents
Name of Supervisor :
Ang Wee Han
Contact Details:
E-mail: [email protected]
Website: http://weehan.science.nus.edu.sg
Telephone: +65 6516 5131
Short Description
Platinum(II) anticancer drug cisplatin is one of the most important
chemotherapeutic drug in clinical use but is limited by its high toxicity and severe sideeffects. Platinum(IV) anticancer prodrugs can overcome these limitations by resisting
premature aquation and binding to essential plasma proteins. Structure activity
relationship studies revealed a close connection between the efficacy of platinum(IV)
complexes with the nature of their axial ligands, which can be modified to enhance the
properties of the prodrug. Our group has developed several techniques to access new
platinum(IV) prodrug modalities with highly customized mode of actions.1,2 Very
recently, we employed this
approach to develop compounds
that can target and illicit an
immunological
response,
thereby achieving the very first
reported multimodal anticancer
platinum agent.3 We have also
unpublished data suggesting this
to be a viable strategy to deliver
cisplatin
specifically
into
targeted cancer cells. The
possibility is endless.
This goal of this PhD project is to apply these general approaches to develop
new and better anticancer prodrugs for targeted chemotherapy. We are particularly
intrigued by the possibility of using our oxime ligation strategy to generate libraries of
platinum(IV)/co-drug conjugates with synergistic modes of action. Candidates should
be interested in synthesis of platinum compounds and working with both nanomaterials
and biological materials. Other more advanced biological techniques such as RT-PCR
and Western Blotting can be acquired on the job.
1
C. F. Chin, Q. Tian, M. I. Setyawati, W. Fang, E. S. Q. Tan, D. T. Leong, W. H. Ang*, Tuning the
activity of platinum(IV) anticancer complexes through asymmetric acylation, J. Med. Chem. 2012, 55,
7571-7582
2
D. Y. Q. Wong, J. Y. Lau, W. H. Ang*, Harnessing chemoselective imine ligation for tethering
bioactive molecules to platinum(IV) prodrugs, Dalton Trans. 2012, 41, 6104-6111
3
D. Y. Q. Wong, C. H. F. Yeo, and W. H. Ang*, Immuno-Chemotherapeutic Platinum(IV) Prodrugs of
Cisplatin as Multimodal Anticancer Agents, Angew. Chem. Int. Ed. 2014, 26, 6752-6756