Anticalin
Encyclopedia
Anticalins are artificial proteins that are able to bind to antigen
s, either to proteins or to small molecules. They are not structurally related to antibodies, which makes them a type of antibody mimetic
. Instead, they are derived from human lipocalin
s which are a family of naturally binding proteins. Anticalins are being used in lieu of monoclonal antibodies
, but are about eight times smaller with a size of about 180 amino acid
s and a mass of about 20 kDa
.
While antibodies and most other antibody mimetics can only be directed at macromolecule
s like proteins, anticalins are able to selectively bind to small molecules as well.
They were mainly developed at the University of Technology Munich and are currently used as research tools. Diagnostic and therapeutic applications, including the use for targeted drug delivery
, are being aimed at. The underlying technology was nominated for the German Future Prize
in 2004.
The main structure of anticalins is identical to wild type lipocalins. Conformational deviations are primarily located in the four loops reaching in the ligand binding site. Mutagenesis
of amino acids at the binding site allows for changing the affinity and selectivity.
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s, either to proteins or to small molecules. They are not structurally related to antibodies, which makes them a type of antibody mimetic
Antibody mimetic
Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens, but that are not structurally related to antibodies. They are usually artificial peptides or proteins with a molar mass of about 3 to 20 kDa...
. Instead, they are derived from human lipocalin
Lipocalin
The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture...
s which are a family of naturally binding proteins. Anticalins are being used in lieu of monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
, but are about eight times smaller with a size of about 180 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s and a mass of about 20 kDa
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...
.
Properties
Anticalins have better tissue penetration than antibodies and are stable at temperatures up to 70 °C. Unlike antibodies, they can be produced in bacterial cells like E. coli in large amounts.While antibodies and most other antibody mimetics can only be directed at macromolecule
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
s like proteins, anticalins are able to selectively bind to small molecules as well.
They were mainly developed at the University of Technology Munich and are currently used as research tools. Diagnostic and therapeutic applications, including the use for targeted drug delivery
Targeted drug delivery
Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. The goal of a targeted drug delivery system is to prolong, localize, target...
, are being aimed at. The underlying technology was nominated for the German Future Prize
German Future Prize
The German Future Prize award is considered one of the most prestigious conferred for science and innovation within Germany. The award is worth 250,000 euros and is more than a scientific prize, it helps to identify projects which not only are of high scientific value, but which have concrete...
in 2004.
Structure
Characteristic for anticalins is their barrel structure formed by eight antiparallel β-strands pairwise connected by loops and an attached α-helix.The main structure of anticalins is identical to wild type lipocalins. Conformational deviations are primarily located in the four loops reaching in the ligand binding site. Mutagenesis
Mutagenesis
Mutagenesis is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures...
of amino acids at the binding site allows for changing the affinity and selectivity.