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

In IEDM 2016 Keynote, Leti CEO Says ‘Hyperconnectivity’, Human-focused Research and the IOT Promise Profound, Positive Changes December 7th, 2016

Leti IEDM 2016 Paper Clarifies Correlation between Endurance, Window Margin and Retention in RRAM for First Time: Paper Presented at IEDM 2016 Offers Ways to Reconcile High-cycling Requirements and Instability at High Temperatures in Resistive RAM December 6th, 2016

Tokyo Institute of Technology research: 3D solutions to energy savings in silicon power transistors December 6th, 2016

Physicists decipher electronic properties of materials in work that may change transistors December 6th, 2016

Govt.-Legislation/Regulation/Funding/Policy

Physicists decipher electronic properties of materials in work that may change transistors December 6th, 2016

Construction of practical quantum computers radically simplified: Scientists invent ground-breaking new method that puts quantum computers within reach December 5th, 2016

Shape matters when light meets atom: Mapping the interaction of a single atom with a single photon may inform design of quantum devices December 4th, 2016

Research Study: MetaSOLTM Shatters Solar Panel Efficiency Forecasts with Innovative New Coating: Coating Provides 1.2 Percent Absolute Enhancement to Triple Junction Solar Cells December 2nd, 2016

Nanomedicine

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Journal Nanotechnology Progress International (JONPI) Volume 6, issue 2 coming out soon! December 5th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Nanobiotix Provides Update on Global Development of Lead Product NBTXR3: Seven clinical trials across the world: More than 2/3 of STS patients recruited in the “act.in.sarc” Phase II/III trial: Phase I/II prostate cancer trial now recruiting in the U.S. November 28th, 2016

Discoveries

Leti IEDM 2016 Paper Clarifies Correlation between Endurance, Window Margin and Retention in RRAM for First Time: Paper Presented at IEDM 2016 Offers Ways to Reconcile High-cycling Requirements and Instability at High Temperatures in Resistive RAM December 6th, 2016

Tokyo Institute of Technology research: 3D solutions to energy savings in silicon power transistors December 6th, 2016

Physicists decipher electronic properties of materials in work that may change transistors December 6th, 2016

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Announcements

In IEDM 2016 Keynote, Leti CEO Says ‘Hyperconnectivity’, Human-focused Research and the IOT Promise Profound, Positive Changes December 7th, 2016

Leti IEDM 2016 Paper Clarifies Correlation between Endurance, Window Margin and Retention in RRAM for First Time: Paper Presented at IEDM 2016 Offers Ways to Reconcile High-cycling Requirements and Instability at High Temperatures in Resistive RAM December 6th, 2016

Tokyo Institute of Technology research: 3D solutions to energy savings in silicon power transistors December 6th, 2016

Physicists decipher electronic properties of materials in work that may change transistors December 6th, 2016

Research partnerships

Deep insights from surface reactions: Researchers use Stampede supercomputer to study new chemical sensing methods, desalination and bacterial energy production December 2nd, 2016

Quantum obstacle course changes material from superconductor to insulator December 1st, 2016

Novel silicon etching technique crafts 3-D gradient refractive index micro-optics November 28th, 2016

Single photon converter -- a key component of quantum internet November 28th, 2016

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