1. Small Molecule-DNA Hybrids (SMDHs) for Cancer Therapy
Andrew Kim
Nguyen Group
PI: Prof. SonBinh T. Nguyen
Mentor: Dr. Bill Hong
Northwestern University, Posner Fellowship

2. Outline Cancer and Current Treatments Ideal Cancer Therapy Agent
Small-Molecule DNA Hybrids (SMDHs)
Synthesis of SMDHs
Future Work

3. Cancer and Current Treatments
1.5 million new cases  500 thousand people
Major types of treatment include:
Surgery
Chemotherapy
I think you are going to emphasize ‘targeted therapy” in this slide, but you should think of how you well connect this with the next slide “ideal cancer therapy agent”?

4. Ideal Cancer Therapy Agent
What characteristics does the ideal cancer therapy agent have?
Targeting Agent – Guides drug to specific cancer cells
Multi Drug Molecules – Give synergy effect for cancer treatment
I think the left and the right should be switched as considering the small title. You should ask me how to change these things tomorrow.
Tracking Agent  Targeting Agent (I think targeting agent is correct, but you should double check)
Specific cells  specific cancer cells
Drug molecules  Multi drug molecules; Anticancer drug payload  kill cancer cells
Visual response molecule  monitor drug response
Imaging Agent – Monitors drug response
Multifunctionality

5. One of the Best Cancer Therapy Agents so Far
Antibody-Drug Conjugate (ADC)
Biodegradable Linking Molecule
Targeting Agent (Antibody)
Drug Molecule
Change the title: this is not ours.
e.g.) Emerging targeted therapeutics
Tracking agent Targeting agent (

6. ADC vs. Ideal Cancer Therapy Agent
Targeting Agent
Targeting Agent
Drug Molecule #1
Drug Molecule #1
Drug Molecule #2
It is better to place “SMDH” and “ADC” on each box, respectively. And remove the text below the right box unless it is necessary.
Tracking agent Targeting agent
Imaging Agent

7. Potential Solution for Drug Delivery
Small Molecule-DNA Hybrids (SMDHs) – DNA is conjugated onto a small molecule
The title does not explain the content in this slide. Think of what you are going to tell in this slide and what title should be?
Before adding other entities conjugated complementary DNA strands, SMDH has a single strand DNA (ssDNA), not double strand DNA (dsDNA). Find a figure of ssDNA and replace it with dsDNA.

8. Potential Solution for Drug Delivery
Multifunctionality: Targeting agent, Imaging agent, other drugs
Drug 2
Drug 1
Same as the previous slide. Change the title.
In this slide, dsDNA is correct since complementary DNAs conjugated with other entities hybridize with the ssDNA of the SMDH. But, in your animation, you should show ssDNA first, then dsDNA with other entities.
Drug  Drug 1; Drug  Drug 2
Tracking agent Targeting agent
Targeting Agent
Imaging Agent

9. Potential Solution for Drug Delivery
Multifunctionality: Targeting agent, Imaging agent, other drugs
Drug 2
Drug 1
Same as the previous slide. Change the title.
In this slide, dsDNA is correct since complementary DNAs conjugated with other entities hybridize with the ssDNA of the SMDH. But, in your animation, you should show ssDNA first, then dsDNA with other entities.
Drug  Drug 1; Drug  Drug 2
Tracking agent Targeting agent
Targeting Agent
Imaging Agent

10. Research Goal Goal: Modulate the DNA arms on SMDH. SMDH3 SMDH2 SMDH1
I don’t understand this figure. You should explain me tomorrow.
SMDH3
SMDH2
SMDH1

11. Research Goal Goal: Modulate the DNA arms on SMDH.
Problem with a previous synthesis method
The right illustration and the left HPLC profile should be switched.
SMDH SMDH SMDH1
SMDH3
Limiting factor: no way to control the DNA arms
Chem. Sci., 2014, 5, 1091

12. By adding protecting groups, the DNA arms on SMDHs can be controlled
Solution
= Protecting Group
= DNA strand
By adding protecting groups, the DNA arms on SMDHs can be controlled

13. Outline Cancer and Current Treatments
What are Antibody-Drug Conjugates (ADCs)?
Why use small-molecule DNA Hybrids (SMDHs)?
Synthesis and Protection of SMDHs
Future Work

14. Step 1 – Synthesis of Tetrakis(4-cyanophenyl)methane
CuCN
DMF, 160⁰C, 4h
Tetrakis(4-bromophenyl)methane
Tetrakis(4-cyanophenyl)methane
Hoskins, B. F, et al. J. Am. Chem. SOC. 1990, 112,

15. Step 1 – Synthesis of Tetrakis(4-cyanophenyl)methane2 1 2
Tetrakis(4-cyanophenyl)methane

16. Step 2 – Synthesis of Tetrakis((4-aminomethyl)phenyl)methane
Tetrakis(4-cyanophenyl)methane
Tetrakis((4-aminomethyl)phenyl)methane
Gandhamsetty, N., et al. J. Org. Chem. 2015, 80, 7281−7287

17. Protection of Core
Fluorenylmethyloxycarbonylchloride (Fmoc) - commonly used to protect amine group +
Protected Amine Group

18. Solid Phase DNA Synthesis
DNA synthesizer

19. Solid Phase SMDH synthesis
DNA conjugated onto open branches +
Open branches

20. Future Work
Remove protecting group and conjugate different DNA strands onto SMDH
Small-Molecule DNA Hybrids have the potential to be developed further towards multifunctional cancer therapeutic agents.

21. Acknowledgements
Mentors: Prof. SonBinh Nguyen Bill Hong, Ph.D. Nguyen Group Northwestern University Posner Fellowship

22. Potential Solution for Drug Delivery
Options to vary functional molecules
Drug
Drug
Same as the previous slide. Change the title.
If you want to emphasize in this slide that more drugs can be delivered by a single SMDH, change the small title. Do not just copy and paste the previous one.
Targeting Agent
Drug