1-SOW_Final.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

X-Ray Crystallography Studies of ALDH1A2

Statement of Need and Purpose:

NCATS ETB needs to crystallize two novel small molecules within the enzyme ALDH1A2 to assist in structure-based design in an ongoing medicinal chemistry campaign.

Background Information and Objective:

The National Center for Advancing Translational Sciences (NCATS) is a part of the National Institutes of Health (NIH), with a mission to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. The Early Translational Branch (ETB) is tasked with identifying and developing novel small molecule leads against a wide spectrum of human disease targets, which it accomplishes by screening thousands of small molecules in collaboration with both intra-and extramural researchers.

In pursuit of this goal, NCATS ETB is optimizing small molecules against ALDH1A2. To optimize potency against ALDH1A2 a structure of an early lead within the confines of a pocket in ALDH1A2 will assist in structure-based design by generating models of putative analogs that can be synthesized to improve potency. The work order entails purification of the protein, screening for conditions to obtain crystals of the protein alone or in combination with the cofactor and/or the novel small molecule. Any prospective hit in the crystallization screen will be sent to the synchrotron to obtain data for structure determination. A report of the structure will be then presented to NCATS.

Period of Performance:

12 months ARO.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

Specific Requirements:

The contractor will synthesize and purify ALDH1A2, run a crystallization screen with five (5) ALDH1A2-compound/cofactor combinations, optimize crystallization hits, collect electron density data, and do structure determination modeling.

• Task I: Protein purification

• Task II: Crystallization screen

• Task III: Crystallization hits optimization

• Task IV: Data collection

• Task V: Structure determination

Payments are to be issued upon completion of each above task and delivery of acceptable reporting.

LEVEL OF EFFORT:

Scientist and/or technician with experience in small molecule-protein co-crystallization screening and X-ray shall run the experiment.

GOVERNMENT RESPONSIBILITIES

NCATS will send powders of compounds and information of solubility and any binding.

DELIVERY OR DELIVERABLES

Electronic copy of report as indicated in reporting requirements.

REPORTING REQUIREMENTS

The contractor will be required to first provide a report that details protein synthesis, purification, and characterization. After trying protein crystallization condition contractor will then report results of protein crystallization experiments. Contractor will then conduct experiments to crystallize the small molecules selected by NCATS within the protein, determine structure, and report structure back to

NCATS.

The reporting will be on an ad hoc basis by email and conference calls as results are obtained over a period of 12 months.

OTHER CONSIDERATIONS

Travel:

N/A

Information System Security Plan:

N/A

Data Rights:

Data belongs to NCATS.

Section 508—Electronic and Information Technology Standards:

N/A

Publications and Publicity:

NCATS will decide timeline for disclosure of data via publication or presentation.

Confidentiality of Information:

Data is to be disclosed only to NCATS and is deemed confidential unless instructed by NCATS.