NIH Medicinal Chemistry Postdoctoral Fellowship for Anti-cancer Drug Discovery

Updated: 14 days ago

Position Description:
A postdoctoral fellowship in the field of medicinal chemistry is immediately available to carry out structure-based drug design and hit-to-lead optimization on several promising hits against polo-like kinase 1 (Plk1). Plk1 is an attractive anti-cancer therapeutic target, whose upregulated activity is tightly associated with aggressiveness and poor prognosis for a wide spectrum of human cancers. We performed high throughput screening campaigns at the at the National Center for Advancing Translational Sciences (NCATS) ( ), and isolated a new class of several anti-Plk1 small molecule compounds, whose cocrystal structures have been determined lately. In an effort to discover novel Plk1-targeted anti-cancer therapeutic agents, we have developed an NCI's multifaceted collaboration project by bringing together various expertise, including medicinal chemistry optimization, X-ray crystallography, in silico modeling, pharmacokinetics/pharmacodynamics, and mouse tumorigenesis studies. Once appointed, the fellow will primarily work in the synthetic chemistry lab at NCATS under the direct guidance of Dr. David Maloney ( ), the medicinal chemistry leader at NCATS, and Dr. Kyung Lee ( ) in the Laboratory of Metabolism, NCI, and will have an opportunity to interact with other collaboration teams involved in this interdisciplinary project.

Applicants should have (or expected to receive) a Ph.D. or its equivalent at the time of joining the lab or have achieved the degree less than 3 years ago. Fellows who have an expertise in medicinal chemistry optimization of small molecule inhibitors or X-ray crystallography are encouraged to apply. Salary starts at $51,900 with full health insurance for fellows with no prior postdoctoral training.

To Apply:
Please send CV and three names of references to Dr. Kyung Lee ( )

Selected Publications:
1) Yun, S. -M. et al., 2009. Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1. Nat. Str. & Mol. Biol. 16:876.
2) Liu, F. et al., 2011. Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel. Nat. Chem. Biol. 7:595.
3) Liu, F. et al., 2012. Identification of high affinity polo-like kinase 1 (Plk1) polo-box domain binding peptides using Oxime-based diversification. ACS Chem. Biol. 7:805.
4) Liu, F. et al., 2012. Peptoid-peptide hybrid ligands targeting the polo-box domain of polo-like kinase 1. Chembiochem. 13:1291.
5) Qian W. -J. et al., 2012. Non-proteinogenic amino acids in the pThr-2 position of a pentamer peptide that confer high binding affinity for the polo-box domain (PBD) of polo-like kinase 1 (Plk1). Bioorg Med Chem Lett. 22:7306.
6) Qian, W. -J. et al., 2013. Effects on Polo-like Kinase 1 Polo-box Domain Binding Affinities of Peptides Incurred by Structural Variation at the Phosphoamino Acid Position. Bioorg. & Med. Chem. 21: 3996.
7) Qian, W. -J. et al., 2014. Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high Plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in HeLa cells. Biopolymers 102:444.
8) Qian, W. -J. et al., 2015. Neighbor-directed Histidine N(τ)-Alkylation: A Route to Imidazolium-containing Phosphopeptide Macrocycles. Biopolymers, 104:663
9) Lee, K. S. et al., 2015. Recent advances and new strategies in targeting Plk1 for anticancer therapy. Trends in Pharmacological Sciences. 36:858 (review).

This position is subject to a background investigation. The NIH is dedicated to building a diverse community in its training and employment programs.

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