PMID- 21110345
OWN - NLM
STAT- MEDLINE
DCOM- 20110331
LR  - 20121115
IS  - 1521-4184 (Electronic)
IS  - 0365-6233 (Linking)
VI  - 343
IP  - 11-12
DP  - 2010 Nov
TI  - Functionalization of fatty acid mimetics for solid-phase coupling and subsequent 
      target identification.
PG  - 625-30
LID - 10.1002/ardp.201000091 [doi]
AB  - Fatty acid mimetics such as pirinixic acid (PA) derivatives and 
      2-(phenylthio)alkanoic acid derivatives are drug-like small molecules with an 
      interesting pharmacological profile. Previously, we have characterized PA 
      derivatives (e.g., 1) as dual agonists of peroxisome proliferator-activated 
      receptors (PPARs) alpha and gamma and as inhibitors of microsomal prostaglandin 
      E(2)-synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO). 2-(Phenylthio)alkanoic acids 
      (e.g., 2) were shown to act as highly active and selective PPARalpha agonists. 
      Encouraged by these results, we would like to identify other target proteins and, 
      thereby, further explore the pharmacological profile of these molecules. An 
      elegant method to screen for potential interaction partners is the so-called 
      "protein-fishing" approach. Requirement is coupling of a functionalized small 
      molecule to a solid phase which is used for biological experiments. Ideally, the 
      pharmacophore of the small molecule remains intact as far as possible. Here, we 
      describe the successful design and synthesis of functionalized fatty acid 
      mimetics, thus providing an eligible starting point for solid-phase coupling and 
      subsequent "protein-fishing" experiments.
FAU - Dittrich, Michaela
AU  - Dittrich M
AD  - Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry, ZAFES/LiFF, 
      Germany.
FAU - Zettl, Heiko
AU  - Zettl H
FAU - Schubert-Zsilavecz, Manfred
AU  - Schubert-Zsilavecz M
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Arch Pharm (Weinheim)
JT  - Archiv der Pharmazie
JID - 0330167
RN  - 0 (Carboxylic Acids)
RN  - 0 (Fatty Acids)
RN  - 0 (PPAR alpha)
RN  - 0 (Pyrimidines)
RN  - 86C4MRT55A (pirinixic acid)
SB  - IM
MH  - Carboxylic Acids/*chemical synthesis/chemistry
MH  - Drug Design
MH  - Drug Evaluation, Preclinical/methods
MH  - Fatty Acids/*chemistry
MH  - Humans
MH  - *Molecular Mimicry
MH  - PPAR alpha/*agonists
MH  - Protein Binding
MH  - Pyrimidines/*chemical synthesis/chemistry
EDAT- 2010/11/27 06:00
MHDA- 2011/04/01 06:00
CRDT- 2010/11/27 06:00
PHST- 2010/11/27 06:00 [entrez]
PHST- 2010/11/27 06:00 [pubmed]
PHST- 2011/04/01 06:00 [medline]
AID - 10.1002/ardp.201000091 [doi]
PST - ppublish
SO  - Arch Pharm (Weinheim). 2010 Nov;343(11-12):625-30. doi: 10.1002/ardp.201000091.