Navigation Links
Penn Scientists Engineer Small Molecules to Probe Proteins Deep Inside Cell Membrane

PHILADELPHIA -- Proteins, which form much of the molecular machinery required for life, are the targets of most drug molecules//. One third of all proteins are membrane proteins – embedded within the cell’s fatty outer layer. While scientists can easily study the other two-thirds using such tools as antibodies, they have not had such methods to investigate the membrane-embedded portions of proteins.

To probe the secrets of these seemingly inaccessible proteins, researchers at the University of Pennsylvania School of Medicine have designed peptides that are able to bind to specific regions of transmembrane proteins, using computer algorithms, and information from existing protein sequence and structure databases. This study, which appears in the March 30 issue of Science, looks at how the binding of these designed peptides affects the crucial first steps in blood clotting.

"We can now actually interrogate parts of proteins within the membrane," says senior author William F. DeGrado, PhD, Professor of Biochemistry and Biophysics. "We used computer programs to design small proteins called peptides that can bind to only one of a number of closely related membrane proteins."

The researchers targeted two transmembrane proteins called integrins that influence the behavior of platelets, small blood cells important in clotting. One of these, the áIIba3 integrin, the most prominent integrin on platelets, is involved in making platelet aggregates, an important first step in the clotting process.

The other integrin, called áVa3, behaves much like áIIba3, in that it causes platelets to stick to certain proteins on the outside of the cell. "We wanted to see if we could differentiate between the two integrins using two different peptides – and, in fact, we can," notes co-senior author Joel Bennett, MD, Professor of Medicine, who works with proteins and cells important in clotting.

When the designed peptide is inserted into the plat elet membrane it binds to the portion of the integrin within the membrane, and subsequently perturbs another function in the clotting process downstream. "By having molecules that bind to the membrane-embedded portions of these proteins, we were able to address questions concerning the way that these proteins are regulated to cause clotting," explains co-first author Joanna Slusky, a doctoral student in the DeGrado laboratory.

"Therapeutics derived from this approach are a long way off, but this method allows us to now study these interactions that are so fundamental to the way in which cells cooperate to carry out essential functions," says Bennett. "In the future, this knowledge can provide insights for identifying novel drug targets."


Related medicine news :

1. Scientists plan human cloning clinic in the United States
2. Scientists found ancient Human Germ Killer
3. Scientists locate key hormone involved in appetite control
4. Scientists open the book of life
5. Scientists review SARS
6. Scientists crack dengue fever puzzle
7. Scientists push to lower hidden sodium in food
8. Indian Scientists Make Wide-Ranging Analysis And Annotation Of X Chromosome
9. Scientists have found effective brain regions for deep brain stimulation for Parkinson’s
10. Scientists reveal the secrets of sarcasm
11. Scientists Unveil Mechanism Behind Resistance to Severe Malaria
Post Your Comments:

(Date:12/1/2015)... ... ... Growth in medical payments per workers’ compensation claim in Louisiana slowed from 2011 ... according to a recent study by the Workers Compensation Research Institute (WCRI). , ... per claim with more than seven days of lost time continued to be higher ...
(Date:12/1/2015)... Wayland, MA (PRWEB) , ... December 01, 2015 , ... ... adults has a tattoo — a number even greater among Millennials (a whopping one ... there are more and more people who are dissatisfied with their ink. In fact, ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... technicians must mark the film for accurate interpretation by the radiologist. The marking ... an inventor from Sacramento, Calif., has found a way to alleviate this problem. ...
(Date:12/1/2015)... ... 01, 2015 , ... Next IT Healthcare, the leader in ... this year’s Fierce Innovation Awards: Healthcare Edition, an awards program from the publisher ... in the category of Digital Solutions for its innovative, industry-leading product, Alme Health ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... Effective Post-Affiliation Integration ,” addresses a main “pain point” for merging or aligning ... results, once a deal is signed. This quick-read guidance suggests that failing ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... , Dec. 1, 2015 Relmada Therapeutics, Inc. ... treatment of chronic pain, announced today that the company will ... be held December 1-3 at the Luxe Sunset Boulevard Hotel ... Traversa , CEO of Relmada Therapeutics, will present on Thursday, ... Time). . Please register at least 10 ...
(Date:12/1/2015)... 2015 CytRx Corporation (NASDAQ: CYTR ), ... today announced that it has reached its enrollment target ... 3 clinical trial of aldoxorubicin in patients with previously ... be completed in Q1 2016. The Phase 3 trial is ... Protocol Assessment from the FDA at 79 sites in ...
(Date:12/1/2015)... , Dec. 1, 2015  Today, ... the launch of CareFront, a first-of-its-kind population health ... diagnosed with cancer. Designed to be built into ... cancer patients with resources for their care and ... program also offers tools to help patients understand ...
Breaking Medicine Technology: