PMID- 15027030
OWN - NLM
STAT- MEDLINE
DCOM- 20041019
LR  - 20061115
IS  - 0952-3499 (Print)
IS  - 0952-3499 (Linking)
VI  - 17
IP  - 2
DP  - 2004 Mar-Apr
TI  - Synthesis and receptor binding of IgG1 peptides derived from the IgG Fc region.
PG  - 95-105
AB  - The IgG binding Fcgamma receptors (FcgammaRs) play a key role in defence against 
      pathogens by linking humoral and cell-mediated immune responses. Impaired 
      expression and/or function of FcgammaR may result in the development of 
      pathological autoimmunity. Considering the functions of FcgammaRs, they are 
      potential target molecules for drug design to aim at developing novel 
      anti-inflammatory and immunomodulatory therapies. Previous data mostly obtained 
      by X-ray analysis of ligand-receptor complexes indicate the profound role of the 
      CH2 domain in binding to various FcgammaRs. Our aim was to localize linear 
      segments, which are able to bind and also to modulate the function of the low 
      affinity FcgammaRs, like FcgammaRIIb and FcgammaRIIIa. To this end a set of 
      overlapping octapeptides was prepared corresponding to the 231-298 sequence of 
      IgG1 CH2 domain and tested for binding to human recombinant soluble FcgammaRIIb. 
      Based on these results, a second group of peptides was synthesized and their 
      binding properties to recombinant soluble FcgammaRIIb, as well as to FcgammaRs 
      expressed on the cell surface, was investigated. Here we report that peptide 
      representing the Arg(255)-Ser(267) sequence of IgG1 is implicated in the binding 
      to FcgammaRIIb. In addition we found that peptides corresponding to the 
      Arg(255)-Ser(267), Lys(288)-Ser(298) or Pro(230)-Val(240) when presented in a 
      multimeric form conjugated to branched chain polypeptide in uniformly oriented 
      copies induced the release of TNFalpha, a pro-inflammatory cytokine from MonoMac 
      monocyte cell line. These findings indicate that these conjugated peptides are 
      able to cluster the activating FcgammaRs, and mediate FcgammaR dependent 
      function. Peptide Arg(255)-Ser(267) can also be considered as a lead for further 
      functional studies.
CI  - Copyright 2004 John Wiley & Sons, Ltd.
FAU - Uray, Katalin
AU  - Uray K
AD  - Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eotvos L. 
      University, Budapest 112, PO Box 32, H-1518, Hungary. uray@szerves.chem.elte.hu
FAU - Medgyesi, David
AU  - Medgyesi D
FAU - Hilbert, Agnes
AU  - Hilbert A
FAU - Sarmay, Gabriella
AU  - Sarmay G
FAU - Gergely, Janos
AU  - Gergely J
FAU - Hudecz, Ferenc
AU  - Hudecz F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Recognit
JT  - Journal of molecular recognition : JMR
JID - 9004580
RN  - 0 (Antigens, CD)
RN  - 0 (Fc gamma receptor IIB)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, CD/*metabolism
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid/methods
MH  - Circular Dichroism/methods
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Flow Cytometry/methods
MH  - Humans
MH  - Immunoglobulin G/*metabolism
MH  - Mass Spectrometry/methods
MH  - Molecular Sequence Data
MH  - Oligopeptides/*chemical synthesis/*metabolism
MH  - Protein Conformation
MH  - Receptors, IgG/*metabolism
EDAT- 2004/03/18 05:00
MHDA- 2004/10/20 09:00
CRDT- 2004/03/18 05:00
PHST- 2004/03/18 05:00 [pubmed]
PHST- 2004/10/20 09:00 [medline]
PHST- 2004/03/18 05:00 [entrez]
AID - 10.1002/jmr.652 [doi]
PST - ppublish
SO  - J Mol Recognit. 2004 Mar-Apr;17(2):95-105. doi: 10.1002/jmr.652.