LI-COR offers click chemistry reagents / dyes

Li-Cor, the company of "environmental and biotechnology research systems", started to offer click chemistry reagents. 

They combined click chemistry with its unique long-wavelength Infrared dyes. Dyes include: IRDye 800CW, TRDye 680RD, IRDye 650. Click chemistry gourps include: dibenzocyclooctyne (DBCO), azide and alkyne. The coupling of above (3x3) generated 9 reagents - for click chemistry in the field of in vitro or in vivo labeling and tracking of biomolecules. Options are available with copper-catalyzed and copper-free versions of click chemistry. 

A webinar is provided for viewers.

Nicholas Turro and the legacy

Nicholas Turro died on November 24, 2012. 

Many of us learned from his photochemistry book, watched his photochemistry videos, met him in person, listened to his presentation on supramolecular photochemistry, and read his recent work on the applications of click chemistry. 

Dr Turro is a truly classy figure in many ways: one of the giants of modern photochemistry;  leader and trail-blazer of creative research in new fields; excellent teacher, educator and lecturer to many levels; superb book writer and natural presenter; father of the large "Turro" academic family; member of NAS and AAAS; recipient of many elite awards. 

A big loss and many will miss him. 



    

Click chemistry in single molecule sequencing

Well, click chemistry has come to single molecule sequencing, one of the hottest spots in modern biotechnology. Pacific Biosciences has demonstrated the sensitive and specific single molecule sequencing of 5-hydroxylmethylcytosine in DNA. Here it is summarized:

Nature Methods, 2012, 9(1), 75

Click chemistry in solving protein 3-D structures

Long live protein chemistry! Early days saw the use of cross-linking reagents such as DCC to lock in spatially adjacent amino groups within proteins. Nowadays the progress of mass spectrometry and proteomics has greatly enhanced the ability to study protein 3-D structures and protein interactions. Here a group of researchers went to click chemistry for additional assistance. Anal Chem 2012, 2662

See the scheme:

Versita plans ambitious Click Chemistry Publication

"Versita, Emerging Science Publishers", has planned an electronic journal for click chemistry. 

In its statement, it intends to be :

1. the first, main option, central and most authoritative publication in click chemistry

2. a new hub, new forum and breeding ground for collaborations between disciplines united by the philosophy of click chemistry 

Journal Editor   Dominic V. McGrath, Universityof Arizona, USA
ISSN: 2299-3932 (electronic version); 
Owner: Versita, Warsaw, Poland
Publisher: Versita, Warsaw, Poland

Ambitious yet challenging, since there exist similar virtual publication channels already. 

Good luck!

                                                                                           

Click chemistry, condensed

We like short meetings, short waiting lines, fast foods, right? How about a new 3-page description of the status of click chemistry? Highly recommend this article.

R&D, 10/10/2012, Thundimadathil, "New reactions with click chemistry: simple and elegant chemical reactions have far-reaching applications in R&D"

This short account covers the most significant key information on click chemistry, in a extremely condensed manner. Lots of admiration for the author's ability to deliver so much info in so little space. 

Best of all - how wonderful is this: "Due to the simplicity of click reactions, biochemists and molecular biologists are able to make complex molecular systems without much bothering about the synthetic chemistry. Click chemistry is approaching the level of ready-made chemistry as many kits are already available in the market for an easy mix and shake approach"  

Enamine click chemistry libraries: Azides and terminal acetylenes

Enamine claims to be the "World largest collection of tangible building blocks and fragments for drug discovery". 

Related to click chemistry, the numbers of tangible structures for azides and terminal acetylenes are 3100 and 9200, respectively. These are estimated to be reliably and quickly synthesized as libraries.

A large existing library of Azides for click chemistry is available and has been used by researchers and companies alike. 

One could use acetylene libraries for screening of candidates. The selected ones could be reacted with azides libraries to create a pool for further screening. 

In other applications one may modify the molecule of interest with one of the above two functional groups and subject it to the other FG libraries for creating a library for further screening or property improvement.

                                                          

Sharpless click chemistry talk at Nobel Campus

July 1-4, 2012. “Southern Catalonia Nobel Campus” was held at The Campus of International Excellence Southern Catalonia, Spain.

“Chemistry for Life”, one hundred young researchers have been chosen in this unique experience to interact with the 6 Nobel laureates: Sidney Altman, Ryoji Noyori, Barry Sharpless, Aaron Ciechanover, Richard R. Schrock and Ada E. Yonath. Also there were the leaders and scientists from industrial world.

A talk by Barry Sharpless covers many topics including click chemistry. Many seemingly random and scattered thoughts may better be heart-felt when one has gained quite some experience into the research career. Say, illusions, astronomical number of possible compounds, function, fishing, on-water reactions, German chemistry tradition, the huge wealth of chemistry in place today, Invitrogen Click-It, etc.

         

Bertozzi: bioorthogonal & click chemistry out of curiosity

A sum-up Lecture on bioorthogonal chemistry by Bertozzi@ Kavli Foundation during ACS Spring 2012 National Meeting in San Diego on March 26, 2012.

"Bioorthogonal chemistry is literally chemistry for life"

Bioorthogonal chemistry and click chemistry owe the debt to the curiosity-driven rather than problem-driven discoveries by two German scientists, Hermann Staudinger & Rolf Huisgen, nearly a century ago. "Without some curiosity-driven research we won't leave much of a legacy for the next generation of scientists".

Bertozzie coined bioorthogonal chemistry decade ago to probe "biomolecules within their native habitats, that is, in cells, or even better, live organisms". The group developed first bioorthogonal reaction, Staudinger ligation, slow for most biological processes. Sharpless CuACC is 25 times faster than Staudinger but with copper toxicity. Copper-free click chemistry, DIFO, combines biocompatibility of Staudinger ligation with fast kinetics of triazol click chemistry. 

                                

Stability & reactivity, copper-free click chemistry

JACS 2012, Angew. Chem. Int. Ed. 2012, 51, 2443


A contribution from Bertozzi group, on the stability and reactivity of cycloalkynes 

Bioorthogaonal chemistry: stable while fast reacting in highly functionalized environment
Rapid reaction kinetics, high specificity, good stability, low side-reactivity
activating vs deactivatiing modifications: ring size (relaxing or strain), electronic factors 
(electron with-drawing, hybridization patterns), stabilizing large atoms as sulfur / Silicon etc.
Cu-free click chemistry, cycloaddition between azides and cyclooctynes
Stability and reactivity can be fine-tuned 
                       

Click chemistry on hair 2

Here is the click chemistry to be applied in the salons :))

Click chemistry on hair 1

Poly. Chem. 2012, 3, 1461


Finally, click chemistry goes to cosmetic industry,  the fastest-growing industry of all? 


Well, sure thing is that you do need fast, mild, high-yielding, failure-proof, safe reactions 
to be happening in hair salons (on the head). Doe that sound like a "perfect" reaction, in the spirit of click chemistry?


Here comes an interesting one applying two types of thiol-ene click chemistry on hair.


1. Polymerisation of mixed acrylates produced the polymer with acrylate terminal alkene 
and allyl internal alkenes  
2. Thiol-ene click chemistry produced conjugates between polymer terminal alkene and thiol 
groups exposed from hair alpha-keratin
3. Thiol-ene click chemistry produced modification between polymer internal alkene and thiol 
groups from dye -------  or any other fun stuff.

Branched Y-Shaped DNA by Click Chemistry

Bioconjugate Chem., 2012, 23 (4), pp 856–870
DOI: 10.1021/bc300013k

Stepwise and double click chemistry produced branched Y-shaped three-armed DNA. 
Hybridization of branched DNA with complementary oligonucleotides yielded supramolecular assemblies / nanostructures.

Protein methylation study by click chemistry

Bioorthogonal Profiling of Protein Methylation Using Azido Derivative of S-Adenosyl-L-methionine, Minkui Luo, et al, J. Am. Chem. Soc. 2012, 134, 5909-5915
dx.doi.org/10.1021/ja2118333

A few key points:
1. Protein methytransferase transfers methyl group from  S-Adenosyl-L-methionine (SAM) to specific proteins.
2. Selective mutation of a transferase allows its acceptance of modified azido-SAM. 
3. Instead of methyl group, the azido-R group was transferred to specific proteins in cells with above SAM transferase.
4. Copper-free Click chemistry and MS reveal the identity of the specific methylated protein.
5. Therfore, methyltransferase - target protein link is established.  

Antibody-type compounds by iterative in situ click chemistry

Angew. Chem. Int. Ed. 2009, 48, (27) 4944

The work by Heath, Fokin, Sharpless et al is summarized in the above graph. To make a few points:
1. For protein binding, Phage-display peptide aptamers are not as popular as DNA aptamers
2. OBOC (one-bead-one-compound) allows for identity tracking in combinatorial chemistry and ligand selection 
3. Multi-valency or multi-dentate ligands provide superior and amazing binding power than the individual components. Remember EDTA? 
4. Protein binding agents, particularly surface binding ones, almost certainly adopt multiple interactions with the target protein, offering superior binding affinity and / or specificity.
5. Triazole linkage in a peptide may present itself much like an amino acid, in terms of size and hydrogen bonding capacity.
6. The above strategy quickly selected nM affinity in third round, from 500uM in first round. 
7. This iterative strategy effectively "expanded" the size of the library (~0.1 million sequences)
8. In situ click chemistry is guided by the surface binding, pulling alkyne and azide into position for reaction for the realization of fragment-based assembly of high-affinity protein binders.
9. The resulting ligands are water-soluble and stable chemically, biochemically, and thermally.
10. Gram-scale synthesis of the selected sequence is straight-forward using CuAAC. 
11. The binding is off-site (non-active site binding), on surface, and highly selective, the general feature of natural antibody. 

Click chemistry Course & Symposium in Nottingham June 2012

Dr. Jon Moses is organizing a course & symposiumdedicated to click chemistry. It will be held in University Park, University of Nottingham, Nottingham, UK, June 15 – 17, 2012.

According to its website, the event will cover the advances of click chemistry in the following areas: bioconjugation; chemical and fluorescent probes, medicinal chemistry and drug discovery; and material science and polymer chemistry.

A great event for those interested in using click chemistry for their respective applications!   

AutoClickChem: most important progress in click chemistry over years

AutoClickChem
http://autoclick.ucsd.edu
PLos Computational Biology, March 2012, Vol 8, Issue 3, e1002397


This work by Durrant and McCammon comes from the marriage of virtual in silico screening and click chemistry. 


In my opinion, it is the most important / significant progress over the years in the field of click chemistry.  


Firstly, the reaction functional groups are automatically detected and click chemistry is accordingly performed to 
generate a virtual library of compouds. 


Secondly, the the compounds are generated automatically in 3-D and ready for docking into protein crystal structures 
and energetics studies.


Thirdly, this application significantly narrows down the better binders / inhibitors from gigantic theoretical numbers 
to a small workable few or certain top percentage.


Fourthly, those candidates are made by click chemistry with ease and speed in high yields, ready for bench screening.   


The program was examined and evaluated in two cases, acetycholinesterase inhibitor tacrin and Protein Tyrosine 
Phosphatase 1B inhibitors. The results matched experimental well.

The program is freely available and a server-application allows online use without installation.

Click linker length adjustment for enzyme inhibition

Org. Biomol. Chem. 2011, 9, 5373 Selectin of the biological activity of DNJ neoglycoconjugates through click length variation of the side chain


Click chemistry was applied to create neoglycoconjugates from deoxynojirimycin and adamantane,  These were bioassayed against a few enzymes as inhibitors or agonist. 


These molecules featured both very hydrophilic and hydrophobic end groups, joined by triazole groups giving spacers / linkers with different lengths. These allow some specificity in terms of different targeted proteins.     

Nanoparticle heteroconjugation via click chemistry

ACS Nano 2012, 6(1) 310  describes nanoparticle heteroconjunction, summarized in the following graph: 

A few key points:

1. Conjugation of Nanoparticle is less reported

2. Many factors against NP conjugation: large size, slow movement, fewer functional groups, lower effective FG concentration, etc

3. A kinetically "unstoppable" reaction is required, such as CuAAC click chemistry

4. Vast possibilities in terms of varieties and functionalities from NP heteroconjugation

5. Controls validated the click chemistry 

6. Will Cu1+ and Cu2+ be an issue in similar applications?