Simple one-pot synthesis of disulfide fragments for use in disulfide-exchange screening.

Abstract:

:Disulfide exchange screening is a method for evaluating the binding of small molecule fragments to proteins that have at least one accessible cysteine. While operationally simple, it does require a large library of small fragment molecules bearing disulfide-containing side chains. These specialized fragments are not available commercially and this has limited the adoption of the method. We report here a convenient one-pot procedure that enables facile preparation of disulfide screening fragments while also producing less of an environmental impact. The new synthetic method involves the initial formation of symmetric disulfides, followed by a disulfide exchange reaction in which the symmetrical dimer is converted into the final screening fragment by introduction of a solubilizing 'cap'. The method is amenable to parallel synthetic methods and can be carried out in air without the need for the specialized equipment typically required for performing organic synthesis.

journal_name

ACS Comb Sci

authors

Burlingame MA,Tom CT,Renslo AR

doi

10.1021/co200038g

subject

Has Abstract

pub_date

2011-05-09 00:00:00

pages

205-8

issue

3

eissn

2156-8952

issn

2156-8944

journal_volume

13

pub_type

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