From Wikipedia,
the free encyclopedia.
Aptamers are small
molecules that can bind to another
molecule. This makes them
particularly attractive to drug
companies as potential drug
candidates.
More specifically, aptamers can
be classified as:
-
DNA or
RNA aptamers. They consist
of (usually short) strands of
oligonucleotides.
-
Peptide aptamers. They
consist of a short variable
peptide domain, attached at both
end to a protein scaffold.
RNA and DNA aptamers
These aptamers are DNA or RNA
molecules that have been selected
from vast populations of random
sequences, through a combinatorial
approach known as systematic
evolution of ligands by
exponential enrichment (SELEX).
The selected sequences have the
ability to recognize specific
ligands by forming binding pockets
and can bind to nucleic acids,
proteins or small organic
compounds.
Peptide aptamers
Peptide aptamers are proteins
that are designed to interfere
with other protein interactions
inside cells. They consist of a
variable peptide loop attached at
both ends to a protein scaffold.
This double structural constraint
greatly increases the binding
affinity of the peptide aptamer to
levels comparable to an antibody's
(nanomolar range).
The variable loop length is
typically comprised of 10 to 20
amino acids, and the scaffold may
be any protein which have good
solubility and compacity
properties. Currently, the
bacterial protein Thioredoxin-A is
the most used scaffold protein,
the variable loop being inserted
within the reducing active site,
which is a -Cys-Gly-Pro-Cys- loop
in the wild protein, the two
Cysteins lateral chains being able
to form a disulfide bridge.
Peptide aptamers selection can
be made using different systems,
but the most used is currently the
yeast
two-hybrid system.
Selection of Ligand Regulated
Peptide Aptamers (LiRPAs) has been
demonstrated. By displaying 7
amino acid peptides from a novel
scaffold protein based on the
trimeric FKBP-rapamycin-FRB
structure, interaction between the
randomized peptide and target
molecule can be controlled by the
small molecule Rapamycin or
non-immunosuppressive analogs.
References
- Bock LC, Griffin LC, Latham
JA, Vermaas EH, Toole JJ,
"Selection of single-stranded
DNA molecules that bind and
inhibit human thrombin.",
Nature, 1992 Feb
6,355(6360):564-6
PMID: 1741036
- Hoppe-Seyler F, Butz K
"Peptide aptamers: powerful new
tools for molecular medicine.",
J Mol Med.
2000;78(8):426-30.PMID:
11097111
- Ellington AD, Szostak JW,
"In vitro selection of RNA
molecules that bind specific
ligands.", Nature, 1990
Aug 30;346(6287):818-22.
PMID: 1697402
- Carothers JM, Oestreich SC,
Davis JH, Szostak JW,
"Informational complexity and
functional activity of RNA
structures.", J Am Chem Soc.
2004 Apr 28;126(16):5130-7.
PMID: 15099096
- Binkowski BF, Miller RA,
Belshaw PJ, "Ligand Regulated
Peptides: A general approach for
selection of ligand regulated
peptide-protein interactions"
Chem & Biol. 2005 July, 12 (7)
