PMID- 10359667
OWN - NLM
STAT- MEDLINE
DCOM- 19990802
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 340 ( Pt 3)
IP  - Pt 3
DP  - 1999 Jun 15
TI  - Identification of oligopeptide sequences which inhibit migration induced by a 
      wide range of chemokines.
PG  - 803-11
AB  - We have identified an amino acid sequence, termed peptide 3, corresponding to 
      amino acids 51-62 of the mature human monocyte chemoattractant protein-1 (MCP-1), 
      which inhibits human mononuclear-cell and THP-1-cell migration induced by a wide 
      range of chemokines. For example, peptide 3 inhibited MCP-1-induced THP-1 
      migration in a transwell assay with an ED50 of approx. 8 microM. Peptide 3 binds 
      directly to THP-1 cells with an association constant of approx. 10 microM, and is 
      therefore likely to be a direct receptor antagonist for CC and CXC chemokine 
      receptors. By performing a structure-function analysis of this peptide, we have 
      identified a sequence variant that shows an approx. 3-4-fold greater potency as 
      an inhibitor of chemokine-induced migration [Leu4Ile11 peptide 3 (1-12)]. 
      Furthermore, unlike peptide 3, which binds to the Duffy antigen receptor for 
      chemokines on human erythrocytes with a similar affinity to the specific 
      chemokine receptors on THP-1 cells, the Leu4Ile11 peptide 3 (1-12) sequence 
      variant shows at least 20-fold greater selectivity for the specific receptors. 
      Derivatives of Leu4Ile11 peptide 3 (1-12) are therefore the best candidates among 
      the molecules we have investigated for use as a chemokine inhibitor in vivo.
FAU - Reckless, J
AU  - Reckless J
AD  - Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, 
      Hills Road, Cambridge CB2 2QQ, UK. jr219@mole.bio.cam.ac.uk
FAU - Grainger, D J
AU  - Grainger DJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Duffy antigen binding protein, Plasmodium)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Antigens, Protozoan
MH  - Carrier Proteins/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/chemistry/metabolism/pharmacology
MH  - Chemokines/*antagonists & inhibitors/chemistry/metabolism/pharmacology
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Conserved Sequence/genetics
MH  - Dose-Response Relationship, Drug
MH  - Erythrocytes/cytology/metabolism
MH  - Female
MH  - Humans
MH  - Leukocytes, Mononuclear/cytology/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oligopeptides/chemistry/genetics/metabolism/*pharmacology
MH  - Peptide Fragments/antagonists & inhibitors/chemistry/metabolism/pharmacology
MH  - *Protozoan Proteins
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Chemokine/antagonists & inhibitors/metabolism/physiology
MH  - Sequence Alignment
MH  - Structure-Activity Relationship
MH  - Transforming Growth Factor beta/pharmacology
PMC - PMC1220314
EDAT- 1999/06/09 00:00
MHDA- 1999/06/09 00:01
PMCR- 1999/12/15
CRDT- 1999/06/09 00:00
PHST- 1999/06/09 00:00 [pubmed]
PHST- 1999/06/09 00:01 [medline]
PHST- 1999/06/09 00:00 [entrez]
PHST- 1999/12/15 00:00 [pmc-release]
PST - ppublish
SO  - Biochem J. 1999 Jun 15;340 ( Pt 3)(Pt 3):803-11.