Kyung Soo Lee

US Patent:

20110076693, Mar 31, 2011

Filed:

May 15, 2009

Appl. No.:

12/992887

Inventors:

Kyung S. Lee - Gaithersburg MD, US
Jung Eun Park - Bethesda MD, US

Assignee:

The U.S.A. as Represented by the Secretary , Dept.of Health and Human Services (the Gov.) - Bethesda MD

International Classification:

G01N 33/573
C07K 14/00
C07K 7/06
C07K 7/08
C12Q 1/48
G01N 33/53

US Classification:

435 74, 530325, 530350, 530328, 530326, 530324, 530327, 536 231, 435 15, 435 71

Abstract:

Isolated peptide substrates of Plk1 and nucleic acids encoding these peptides are disclosed. The peptides include two to ten repeats of the amino acid sequence set forth as XXAXXXPLHSTXXXXXXX(SEQ ID NO: 1), in which within each repeat X, X, X, X, X, X, X, X, and Xare each independently any amino acid or no amino acid, and Xand Xare each independently any amino acid. Methods of using these peptides to detect Plk1 activity in a sample are also disclosed. In some examples, the method includes contacting a sample with a disclosed peptide substrate of Plk1 in the presence of adenosine triphosphate, or an analog thereof, for a period of time sufficient for Plk1 to phosphorylate the PBIPtide. The presence and/or amount of the phosphorylated and/or the unphosphorylated peptide is detected, thereby detecting and/or quantitating Plk1 kinase activity in the sample.

US Patent:

20160039872, Feb 11, 2016

Filed:

Mar 14, 2014

Appl. No.:

14/776512

Inventors:

- Rockville MD, US
Jung Eun Park - Bethesda MD, US
Christopher C. Lai - Ellicott City MD, US
James A. Kelley - Silver Spring MD, US
Kyung S. Lee - Gaithersburg MD, US

International Classification:

C07K 7/06
C07F 9/40
C07K 1/06
C07F 9/141

Abstract:

The invention provides novel compounds that may serve as anticancer therapeutics. The compounds of the invention bind to polo-like kinases through the polo-box domain. In certain embodiments, the compounds of the invention are POM-protected peptide derivatives. The use of cationic bis-alkyl his residues in combination with a mono POM-protected pho-phoryl group results in a peptide possessing an overall neutral charge. The peptide derivatives of the invention have achieved both good efficacy and an enhanced bioavailability. The invention also provides methods of use, compositions, and kits thereof. Further, the invention provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.

US Patent:

20140142044, May 22, 2014

Filed:

Apr 12, 2012

Appl. No.:

14/111540

Inventors:

Wenjian Qian - Frederick MD, US
Fa Liu - Indianapolis IN, US
Kyung S. Lee - Gaithersburg MD, US
Jung-Eun Park - Bethesda MD, US

Assignee:

The United States of America, as represented by the Secretary, Department of Health & Human Servic - Rockville MD

International Classification:

C07K 7/06

US Classification:

514 194, 530330, 514 192, 514 193, 514 196, 514 195, 506 18

Abstract:

Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds. The compounds of the invention have potential therapeutic activity in view of their binding and inhibitory activities towards Plk1. They are based on the amino acid sequence PLHSpT (phosphorylated Thr). The PEG moiety, when present, is covalently attached at the N-terminus. The invention also encompasses derivatives having substituents on the Pro and/or the His side chains, substituents on the phosphate group, the replacement of His with Gln, the replacement of Pro with a N-substituted Gly, the replacement of Ser with Ala, as well as HS-pT fragments with N-terminal alkoxycarbonyl group and PLHS fragments with a C-terminal glyco-imino-alkylxyalkylamide group.