Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Antibody Replacements Just a "Click" Away (Special Interest Story)

Abstract:
Chemists at the California Institute of Technology (Caltech) and The Scripps Research Institute (SRI) have developed an innovative technique to create cheap but highly stable chemicals that have the potential to take the place of the antibodies used in many standard medical diagnostic tests. James R. Heath, Ph.D., principal investigator of the Nanosystems Biology Cancer Center at Caltech, one of eight Centers of Cancer Nanotechnology Excellence, and K. Barry Sharpless, Ph.D., SRI, and their colleagues describe the new technique in the journal Angewandte Chemie International Edition.

Antibody Replacements Just a "Click" Away (Special Interest Story)

Bethesda , MD | Posted on August 30th, 2009

Last year, Dr. Heath and his colleagues announced the development of the integrated blood-barcode chip, a diagnostic medical device about the size of a microscope slide that can separate and analyze dozens of proteins using just a pinprick of blood. The barcode chip employed antibodies, which are proteins utilized by the immune system to identify, bind to, and remove particular foreign compounds such as bacteria, viruses, and other proteins.

"The thing that limits us in being able to go to, say, 200 proteins in the barcode chip is that the antibodies used to detect the proteins are unstable and expensive," said Dr. Heath. "We have been frustrated with antibodies for a long time, so we wanted to be able to develop antibody equivalents—what we call protein capture agents—that can bind to a particular protein with very high affinity and selectivity and that pass the following test: You put a powder of them in your car trunk in August in Pasadena, and you come back a year later and they still work."

In the new work, Dr. Heath and his colleagues have developed a protocol to quickly and cheaply make such highly stable compounds, which are composed of short chains of amino acids, or peptides. The technique makes use of the "in situ click chemistry" method introduced by Dr. Sharpless in 2001, in which chemicals are created by joining—or "clicking"—smaller subunits together.

To create a capture agent for a particular protein, the scientists devised a stepwise approach in which the first subunit of the capture agent is identified, and then that unit, plus the protein, is used to identify the second subunit, and so on. For the first subunit, a fluorescent label is added to the protein, which then is incubated with a bead-based library of tens of millions of short-chain peptides, representing all the potential building blocks for the capture agent. When one of those peptides binds to the protein of interest, the fluorescent label is visualized on the bead (red, blue, or green, depending on the type of label), allowing the linked protein-peptide complex to be identified.

That first peptide, which is about one-third of the length of the final capture agent the scientists are trying to make, then is isolated, purified, and modified on one end by the addition of a chemical group called an alkyne. This is the anchor peptide, which then is incubated, together with the same protein, with the bead-based library. The bead-based library now contains peptides that have been chemically modified to contain an azide group at one end. The alkyne group on the added peptide can potentially chemically react with the azide group of the library's peptides to create a new peptide that is now two segments long.

However, the reaction can occur only when the second peptide comes into close contact with the first on the surface of the target protein, which means that both must have affinity for that protein; essentially, the protein itself builds an appropriate capture agent. The two-segment-long peptide then is isolated and purified, "and then we modify the end of that with an alkyne and add it back to the library to produce a three-segment peptide, which is long enough to be both selective for and specific to the target protein," Dr. Heath said.

"What Dr. Heath has shown is that in several iterations, a high-affinity ligand for a protein can be created from blocks that do not bind to the protein all that well; the trick is to repeat the in situ screen several times, and the binding improves with every iteration," noted Dr. Sharpless.

"This is about as simple a type of chemistry as you can imagine," said Dr. Heath. The process, he said, makes "trivial" the "Herculean task of finding molecules that bind selectively and with high affinity to particular proteins. I see no technical reason it couldn't replace any antibody."

####

About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.

The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.

Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.

For more information, please click here

Contacts:
National Cancer Institute
Office of Technology & Industrial Relations
ATTN: NCI Alliance for Nanotechnology in Cancer
Building 31, Room 10A49
31 Center Drive , MSC 2580
Bethesda , MD 20892-2580

Copyright © National Cancer Institute

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

View abstract - “Iterative in situ click chemistry creates antibody-like protein-capture agents”

Related News Press

News and information

Chemists Cook up New Nanomaterial and Imaging Method: Nanomaterials can store all kinds of things, including energy, drugs and other cargo January 19th, 2017

National Space Society Congratulates SpaceX on the Falcon 9's Return to Flight January 19th, 2017

Eric Berger Wins the National Space Society's 2017 Space Pioneer Award for Mass Media January 19th, 2017

Nanometrics to Announce Fourth Quarter and Full Year Financial Results on February 7, 2017 January 19th, 2017

Govt.-Legislation/Regulation/Funding/Policy

'5-D protein fingerprinting' could give insights into Alzheimer's, Parkinson's January 19th, 2017

Strength of hair inspires new materials for body armor January 18th, 2017

Self-assembling particles brighten future of LED lighting January 18th, 2017

Nanoscale view of energy storage January 16th, 2017

Nanomedicine

Chemists Cook up New Nanomaterial and Imaging Method: Nanomaterials can store all kinds of things, including energy, drugs and other cargo January 19th, 2017

'5-D protein fingerprinting' could give insights into Alzheimer's, Parkinson's January 19th, 2017

New active filaments mimic biology to transport nano-cargo: A new design for a fully biocompatible motility engine transports colloidal particles faster than diffusion with active filaments January 11th, 2017

Keystone Nano Announces FDA Approval Of Investigational New Drug Application For Ceramide NanoLiposome For The Improved Treatment Of Cancer January 10th, 2017

Discoveries

Chemists Cook up New Nanomaterial and Imaging Method: Nanomaterials can store all kinds of things, including energy, drugs and other cargo January 19th, 2017

'5-D protein fingerprinting' could give insights into Alzheimer's, Parkinson's January 19th, 2017

Strength of hair inspires new materials for body armor January 18th, 2017

Self-assembling particles brighten future of LED lighting January 18th, 2017

Announcements

Chemists Cook up New Nanomaterial and Imaging Method: Nanomaterials can store all kinds of things, including energy, drugs and other cargo January 19th, 2017

National Space Society Congratulates SpaceX on the Falcon 9's Return to Flight January 19th, 2017

Eric Berger Wins the National Space Society's 2017 Space Pioneer Award for Mass Media January 19th, 2017

Nanometrics to Announce Fourth Quarter and Full Year Financial Results on February 7, 2017 January 19th, 2017

Research partnerships

Chemists Cook up New Nanomaterial and Imaging Method: Nanomaterials can store all kinds of things, including energy, drugs and other cargo January 19th, 2017

Chemistry on the edge: Experiments at Berkeley Lab confirm that structural defects at the periphery are key in catalyst function January 13th, 2017

Recreating conditions inside stars with compact lasers: Scientists offer a new path to creating the extreme conditions found in stars, using ultra-short laser pulses irradiating nanowires January 12th, 2017

Zeroing in on the true nature of fluids within nanocapillaries: While exploring the behavior of fluids at the nanoscale, a group of researchers at the French National Center for Scientific Research discovered a peculiar state of fluid mixtures contained in microscopic channels January 11th, 2017

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project