Catalyst-free Ligation Using Metal-free, Light-induced Click Reaction
- Detailed Technology Description
- Application(Product)Methodsand compositions to promote difficult chemical reactions, especially involvingliving organisms ProblemsAddressed (benefits/advantages)Connection(or ligation) of two fragments to make a larger molecule or structure is oftenachieved with the help of the so-called "click chemistry". This termis used to describe a set of bimolecular reactions that meet the followingcriteria: reactions should be wide in scope but selective; produce high yieldof the product, proceed with reasonable rate under mild conditions; andtolerate broad range of solvents. Among known click reactions is the reactionof azides with acetylenes. The formation of 1,2,3-triazoles in 1,3-dipolarcycloaddition of azides to triple bond is known, but 'because the activationenergy of acetylene-azide cycloaddition is relatively high (ΔG‡ ~26 kcal/mol),the reaction is very slow under ambient conditions. The utility of the reactionof azides with alkynes was expanded by the discovery of Cu (I) ca-talysis.1,3-cycloaddition of azides to terminal acetylenes in the presence of catalyticamounts of cuprous salts is facile at room temperature in organic or aqueoussolutions. The copper-catalyzed version of the acetylene- azide cycloaddition(a.k.a. azide click reaction) found a broad range of applications from microelectronicsto virus labeling, to drug development. However, the use of cytotoxic Cu (I)catalyst has largely precluded application of this click reaction in livingsystems. Catalyst-free 1,3-dipolarcycloaddition of azides to cyclooctynes has made possible a bio-compatible versionof the azide click reaction. The triple bond incorporated in an eight-memberedring is apparently already bent into the transition state-resembling geometry,thus reducing the activation barrier. New methods for ligating fragments tomake a larger molecule or structure and allow the use of these structures for invivo studies are needed.
- *Abstract
-
TechnologySummary
UGA researchers have developed methods andcompositions the for light-induced ligation of molecules, without the use of acatalyst. In particular, the technology relates to the generation of reactiveacety-lenes (e.g., cyclooctyne) produced by light-induced eliminationfrom proprietary compositions. This photochemical ligation method provides amethod of linking two molecules triggered by the photo-chemical generation ofcyclic alkynes (e.g., cyclooctynes) from corresponding proprietary startingmate-rials. The catalyst-free method has successfully been used in severalexperiments including the fast, photo-induced, labeling of live cells. Thereactive species can bear multiple substituents such as fluores-cent tags,biotin, carbohydrates, isotopically labeled fragments, antibiotic molecules,and PEG, among others and/or contain a heteroatom in its structure. The methodand compositions are also suitable reagents for light-induced π metathesis,cycloaddition, Paulson-Khand and other reactions.
Advantages and Some PotentialApplications
Fast, easy synthesis and inexpensive
Versatile (facilitates/promotes a myriad of light-inducedalkene/alkyne reactions with many substrates)
Applicable to labeling of live cells, possibly includingGram-negative baceria
Applicable to the synthesis of novel materials and in substratepatterning
Catalyst-free
Reactive alkynes can contain other groups of interest
.
Inventor
Dr.Vladimir Popik
TechnologyDevelopment and IP Status
Production in lab scale hasbeen optimized. Reactions are scalable.
Issued US Patents 8,258,347; 8 ,426,649 ; 8,541, 625
- Country/Region
- USA
