PMID- 16680799
OWN - NLM
STAT- MEDLINE
DCOM- 20060925
LR  - 20061115
IS  - 1075-2617 (Print)
IS  - 1075-2617 (Linking)
VI  - 12
IP  - 8
DP  - 2006 Aug
TI  - Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor.
PG  - 515-24
AB  - Brain-derived neurotrophic factor (BDNF) is a protein that promotes the survival 
      of neurons. It is widely thought to possess clinical potential for the treatment 
      of neurodegenerative diseases, and in recent years, has been found to play a role 
      in the pathogenesis of some tumours. BDNF is thought to bind to its cellular 
      receptors trkB and p75(NTR) primarily by way of solvent-exposed loops on the BDNF 
      dimer. In this paper, we describe our recent progress towards the development of 
      small peptides as mimetics and inhibitors of BDNF. Two classes of peptides were 
      prepared: disulphide-constrained monomeric monocyclic peptides designed to mimic 
      a single solvent-exposed loop; and homo- and heterodimeric bicyclic peptides 
      designed to mimic pairs of loops. Each peptide was examined in cultures of 
      embryonic chick dorsal root ganglion sensory neurons, both alone, and in 
      competition with BDNF. All peptides were found to inhibit BDNF-mediated neuronal 
      survival, while one--a dimeric peptide based on the two loop 4 regions of 
      BDNF--behaved as a partial BDNF-like agonist. The work described in this paper 
      supports the proposed receptor-binding role of loops 1, 2, and 4 of BDNF, and 
      provides valuable steps towards our long-term goal of developing BDNF mimetics 
      and inhibitors for clinical use.
CI  - Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.
FAU - Fletcher, Jordan M
AU  - Fletcher JM
AD  - Department of Pharmacology, The University of Melbourne, Victoria 3010, 
      Australia.
FAU - Hughes, Richard A
AU  - Hughes RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pept Sci
JT  - Journal of peptide science : an official publication of the European Peptide 
      Society
JID - 9506309
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - Analysis of Variance
MH  - Animals
MH  - Biomimetics/*methods
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/chemistry/*metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chick Embryo
MH  - Dimerization
MH  - Ganglia, Spinal/cytology/drug effects
MH  - Models, Chemical
MH  - Models, Molecular
MH  - Neurons, Afferent/cytology/drug effects
MH  - Peptides/*chemical synthesis/chemistry/pharmacology
MH  - Protein Binding
MH  - Protein Structure, Quaternary
EDAT- 2006/05/09 09:00
MHDA- 2006/09/26 09:00
CRDT- 2006/05/09 09:00
PHST- 2006/05/09 09:00 [pubmed]
PHST- 2006/09/26 09:00 [medline]
PHST- 2006/05/09 09:00 [entrez]
AID - 10.1002/psc.760 [doi]
PST - ppublish
SO  - J Pept Sci. 2006 Aug;12(8):515-24. doi: 10.1002/psc.760.