Description:
 
Background
As exemplified by thiolate-ene “click” chemistry, the unique properties of thiolates enable highly selective reactions. Dithiol-diene reaction partners can template high order structures and are employed (in vitro) in polymer syntheses, in biochemical probes, and to stabilize proteins. Unfortunately, ‑enes react with a myriad of essential protein cysteine residues, resulting in toxicity that limits their applicability in vivo. 
 
Technology Overview
This invention has a more biocompatible method for crosslinking thiolate pairs. Northeastern University researchers reasoned that cyclic thiosulfinates – S-oxo derivatives of well-tolerated cyclic disulfide natural products – would selectively crosslink dithiols by the following mechanism. 
A nucleophilic attack by thiolateA upon the thiosulfinate disulfide results in thiolate-disulfide interchange concomitant to ring cleavage, and a disulfide tethered terminal sulfenic acid moiety. Next, a nucleophilic attack by thiolateB on the sulfenic sulfur results in the formation of a second disulfide bond coupled to the release of water and a crosslink. This could include crosslinking two molecules via their two (respective) thiol functionalities, using cyclic thiosulfinates or crosslinking two molecules, via their respective cyclic thiosulfinate functionalities, using a crosslinker endowed with a pair of dithiols. 
 
Benefits
- Analogous reactions to using dienes (or other commonly used electrophiles) to crosslink thiols 
- Most of the attributes of click chemistry including orthogonality with other protein functional groups, high reaction yields, rapid reactions, stereoselectivity, compatibility with aqueous solvents, and a ring strain-dependence that is orders of magnitude higher than existing period 2 element systems 
 
Applications
- Biopolymers
- Self-healing biopolymers
- Biocompatible hydrogels
- Functionalized surfaces
- Wound healing
- Surgical site healing
- Implants
 
Opportunity
- License
- Partnering
- Research collaboration
Patent Information:
For Information, Contact:
Mark Saulich
Associate Director of Commercialization
Northeastern University
m.saulich@northeastern.edu
Inventors:
Jeffrey Agar
Keywords: