PMID- 17981839
OWN - NLM
STAT- MEDLINE
DCOM- 20080118
LR  - 20211020
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 35
IP  - 22
DP  - 2007
TI  - Exploring the sequence space of a DNA aptamer using microarrays.
PG  - 7626-35
AB  - The relationship between sequence and binding properties of an aptamer for 
      immunoglobulin E (IgE) was investigated using custom DNA microarrays. Single, 
      double and some triple mutations of the aptamer sequence were created to evaluate 
      the importance of specific base composition on aptamer binding. The majority of 
      the positions in the aptamer sequence were found to be immutable, with changes at 
      these positions resulting in more than a 100-fold decrease in binding affinity. 
      Improvements in binding were observed by altering the stem region of the aptamer, 
      suggesting that it plays a significant role in binding. Results obtained for the 
      various mutations were used to estimate the information content and the 
      probability of finding a functional aptamer sequence by selection from a random 
      library. For the IgE-binding aptamer, this probability is on the order of 10(-10) 
      to 10(-9). Results obtained for the double and triple mutations also show that 
      there are no compensatory mutations within the space defined by those mutations. 
      Apparently, at least for this particular aptamer, the functional sequence space 
      can be represented as a rugged landscape with sharp peaks defined by highly 
      constrained base compositions. This makes the rational optimization of aptamer 
      sequences using step-wise mutagenesis approaches very challenging.
FAU - Katilius, Evaldas
AU  - Katilius E
AD  - Center for BioOptical Nanotechnology, The Biodesign Institute and the Department 
      of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-5201, 
      USA. ekatilius@asu.edu
FAU - Flores, Carole
AU  - Flores C
FAU - Woodbury, Neal W
AU  - Woodbury NW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071102
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Aptamers, Nucleotide)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Aptamers, Nucleotide/*chemistry
MH  - Base Sequence
MH  - Fluorescence
MH  - Humans
MH  - Immunoglobulin E/*metabolism
MH  - Mutation
MH  - *Oligonucleotide Array Sequence Analysis
MH  - Protein Binding
PMC - PMC2190713
EDAT- 2007/11/06 09:00
MHDA- 2008/01/19 09:00
PMCR- 2007/11/02
CRDT- 2007/11/06 09:00
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2008/01/19 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
PHST- 2007/11/02 00:00 [pmc-release]
AID - gkm922 [pii]
AID - 10.1093/nar/gkm922 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2007;35(22):7626-35. doi: 10.1093/nar/gkm922. Epub 2007 Nov 2.