22-005676 SOW (official).pdf

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

STATEMENT OF WORK

(SOW)

GENERAL INFORMATION

Title of Project:

X-ray Co-crystal Structure and SPR Studies

Statement of Need and Purpose:

NCATS is in need of enzyme-small molecule co-crystal structures and binding data against the bacterial glucoronidase H11G11 and RgGUS, and the methyl transferase GNMT. This will enable structure-based drug design while optimizing compounds in medicinal chemistry campaigns.

Background Information and Objective:

Structure guided drug design forms a central strategy in optimizing compounds in medicinal chemistry campaigns in target-based drug discovery. We are optimizing structurally different compounds or small molecules against the bacterial glucoronidases H11G11 and RgGUS, and the methyl transferase GNMT. Very recently XTAL BioStructures, Inc. (now Schrödinger after its acquisition) secured the protein RgGUS and successfully solved crystal structure of the isolated protein, co-crystal structures of two distinct chemotypes in combination with an enzyme substrate. This work was initiated with a previous purchasing order with contract This partially completed work has proven the XTAL is able to obtain co-crystals structures of proteins with small molecules provided by NCATS. This promising work is required to continue to aid in the design of subsequent compounds from the same chemical series that have been crystalized and others structurally distinct compounds.

In addition to obtaining co-crystal structures NCATS needs to extend the initial contract to also obtain critical enzyme-small molecule binding parameters (such as Kd, kon, koff) through surface plasmon resonance (SPR) technology; it is important that this work is done at XTAL (Schrodinger) who already have the protein and small molecule with them from co-crystal structural work.

The same workflow of obtaining cocrystal structures and binding data will be extended to the methyltransferase GNMT.

Period of Performance:

The Period of Performance is anticipated to be 12-months from date of award.

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:

Protein required for this work is already available with vendor; this was enabled via prior contract. New crystal structures will be obtained using the same protein and same techniques.

Same protein will be used for new binding data.

The project consists of two parts.

1) Crystallization, compound soaking, synchrotron X-ray evaluation, and X-ray structure determination of RgGUS in complex with ligands

2) The SPR options below are examples of the work to be completed. The amount of compounds tested may change.

- Optional Assay #3: Competitive binding measurements (5 test compounds)

- Optional Assay #2: Binding measurements (12 test compounds)

- Optional Assay #3: Competitive binding measurements (5 test compounds)

LEVEL OF EFFORT:

The Contractor shall use best efforts in providing services as described in the requirements above.

GOVERNMENT RESPONSIBILITIES

NCATS will supply compounds and target compounds to the vendor.

DELIVERY OR DELIVERABLES

Periodic reports with detailed description of experimental methods, results, and conclusions via emails and/or video conference calls showing progress in protein production, purification, and determination of structure and binding data.

REPORTING REQUIREMENTS

Progress reports with deliverables (mentioned above) every week between vendor and

NCATS.

OTHER CONSIDERATIONS

Travel:

N/A

Key Personnel:

Information System Security Plan:

Data Rights:

Data belongs to NCATS

Section 508—Electronic and Information Technology Standards:

N/A

Publications and Publicity:

Contractor will not publish any information without informing NCATS. All information is confidential and NCATS will solely determine date for publication or publicity or patenting.

Confidentiality of Information:

All information shared between NCATS and contractor is confidential. The time or method for publication will be determined by NCATS.

All information shared between NCATS and contractor is confidential. The time or method for publication will be determined by NCATS.