PMID- 21963635
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20190706
IS  - 1347-5223 (Electronic)
IS  - 0009-2363 (Linking)
VI  - 59
IP  - 10
DP  - 2011
TI  - Computational analysis on the binding of epitope peptide to human leukocyte 
      antigen class I molecule A*2402 subtype.
PG  - 1254-62
AB  - Immunological response induced by small amino peptide has attracted much recent 
      attention in the field of immunotherapy. Wilms' tumor (WT1) protein is one of the 
      potent tumor antigens inducing immunological response in mouse and human, because 
      WT1 is over expressed in many types of leukemia and various kinds of solid 
      tumors. A 9-mer peptide encoded in WT1 protein (CMTWNQMNL; amino acid 235-243) is 
      known to serve as antigenic peptide for human leukocyte antigen (HLA)-A*2402 
      molecule. It was reported that the replacement of the second amino residue, which 
      is deeply responsible for the peptide binding to HLA, induced strong 
      immunological response compared to the natural peptide. In this study, 19 kinds 
      of single amino substitutions were introduced at position 2 of this 9-mer WT1 
      peptide. We performed molecular dynamics simulation on the complex of each of WT1 
      epitope peptides and HLA-beta2 micro globulin (beta2m) molecule, and subsequently 
      estimated the binding affinity using molecular mechanics/generalized-Born surface 
      area method combined with normal mode analysis. Our computation indicated that 
      the peptide containing M2Y or M2W mutation showed high binding affinity to the 
      HLA-beta2m molecule as well as the natural peptide. We have also examined the role 
      of the residue at position 2 in peptide binding to HLA-beta2m. The calculation 
      showed that van der Waals interaction between the side chain of the residue at 
      position 2 and hydrophobic residues inside B-pocket of HLA are important. These 
      findings will be helpful to search other potent peptides that will enhance strong 
      immunological response specific to HLA-A*2402 molecule.
FAU - Mahmood, M D Iqbal
AU  - Mahmood MD
AD  - Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
FAU - Matsuo, Yuri
AU  - Matsuo Y
FAU - Neya, Saburo
AU  - Neya S
FAU - Hoshino, Tyuji
AU  - Hoshino T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Chem Pharm Bull (Tokyo)
JT  - Chemical & pharmaceutical bulletin
JID - 0377775
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - Epitopes/chemistry/immunology/*metabolism
MH  - HLA-A Antigens/chemistry/genetics/immunology/*metabolism
MH  - Histocompatibility Antigens Class II/chemistry/immunology/*metabolism
MH  - Humans
MH  - Immunotherapy
MH  - Leukocytes/immunology/metabolism/pathology
MH  - Mice
MH  - *Molecular Dynamics Simulation
MH  - Molecular Structure
MH  - Neoplasms/immunology/*therapy
MH  - Peptide Fragments/immunology/metabolism
MH  - Peptides/chemistry/immunology/metabolism
MH  - Protein Binding/immunology
MH  - *Software
EDAT- 2011/10/04 06:00
MHDA- 2012/06/30 06:00
CRDT- 2011/10/04 06:00
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
AID - JST.JSTAGE/cpb/59.1254 [pii]
AID - 10.1248/cpb.59.1254 [doi]
PST - ppublish
SO  - Chem Pharm Bull (Tokyo). 2011;59(10):1254-62. doi: 10.1248/cpb.59.1254.